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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

DARZALEX® (daratumumab)

Medical Information

DARZALEX - MMY2004 (GRIFFIN) Study

Last Updated: 07/24/2025

Click on the following links to related sections within the document: GRIFFIN (MMY2004) Study Overview, Part 1: Results, Part 2: Primary and Updated Analyses Results, and Part 2: Final Analysis Results.
Abbreviations: AE, adverse event; ASCT, autologous stem cell transplant; CR, complete response; ≥CR, complete response or better; CrCl, creatinine clearance; DLT, dose-limiting toxicity; ECOG PS, Eastern Cooperative Oncology Group performance status; HDT, high-dose therapy; IMWG, International Myeloma Working Group; IRR, infusion-related reaction; IV, intravenous; MM, multiple myeloma; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; NGS, next-generation sequencing; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; R, lenalidomide; Rd, lenalidomide and dexamethasone; sCR, stringent complete response; TEAE, treatment-emergent AE; VGPR, very good partial response; VRd, bortezomib, lenalidomide, and dexamethasone.
aVoorhees (2017).1 bVoorhees (2019).2 cVoorhees (2020).3 d21-day cycles. e28-day cycles. fVoorhees (2021).4 gLaubach (2021).5 hIncludes the preferred terms of peripheral neuropathy and peripheral sensory neuropathy. iVoorhees (2023).6 jThere were no grade 4/5 IRRs.

SUMMARY

  • DARZALEX is not approved by the regulatory agencies for use in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of multiple myeloma (MM). Janssen does not recommend the use of DARZALEX in a manner that is inconsistent with the approved labeling.
  • GRIFFIN was a 2-part, phase 2 study that evaluated the safety and efficacy of DARZALEX when administered in combination with VRd (D-VRd) in patients with newly diagnosed multiple myeloma (NDMM) eligible for high-dose therapy (HDT) and autologous stem cell transplant (ASCT).1-3
    • Part 1: Voorhees et al (2021)4 reported the final analysis of the safety run-in cohort (N=16) of the GRIFFIN study with a median follow-up of 40.8 months. By the end of D-VRd consolidation, 56.3% patients achieved stringent complete response (sCR), and 50.0% were minimal residual disease (MRD) negative (10-5 threshold). After maintenance, 93.8% patients achieved sCR, and 81.3% patients were MRD negative (10-5 threshold). Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 93.8% of patients. One death from progressive disease (PD) occurred in the patient who did not achieve sCR.
    • Part 2: Voorhees et al (2020)2,3 presented the primary analysis of the randomized portion of this study (n=207). Voorhees et al (2023)6 reported the final efficacy and safety results after all patients completed ≥1 year of follow-up after the end-of-study treatment, died, or withdrew from study participation. The median duration of follow-up was 49.6 months. In the D-VRd vs VRd arm, respectively, sCR was achieved in 67% vs 48% of patients (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.22-3.89; 2-sided P=0.0079) and complete response or better (≥CR) in 83% vs 60% of patients (P=0.0005). At the end of the study, 14% (n/N=15/104) and 10% (n/N=10/103) of patients in the D-VRd and VRd arms, respectively, who were previously MRD positive at the end of the consolidation phase, converted to MRD negative (10-5). In the D-VRd vs VRd arm, the most common (≥10%) grade 3/4 TEAEs were neutropenia (46% vs 23%), lymphopenia (23% in both arms), leukopenia (17% vs 8%), thrombocytopenia (16% vs 9%), pneumonia (12% vs 14%), and hypophosphatemia (10% vs 11%).
  • Rodriguez et al (2022)7 presented a post hoc analysis of the GRIFFIN study at a median follow-up of 38.6 months that assessed the sustained MRD-negativity (lasting ≥6 or ≥12 months) in clinically relevant subgroups as well as among patients with ≥CR. Rates of sustained MRD-negativity (10-5) lasting ≥6 or ≥12 months were higher with D-VRd vs VRd in all clinically relevant subgroups. Similar trends were observed when measured at a higher MRD sensitivity threshold of 10-6, although some variability was observed.
  • Nooka et al (2024)8 reported updated post hoc analysis results by race at the time of final analysis in the overall population with ~2 years of additional follow-up. The median duration of follow-up was 49.6 months. In the D-VRd vs VRd arm, the rate of sCR was 92.9% vs 38.9% in Black patients and 65.1% vs 50.0% in White patients, the rate of MRD-negativity (at 10-5 threshold) was 64.3% vs 22.2% in Black patients and 65.9% vs 31.6% in White patients, and the estimated 48-month progression-free survival (PFS) rate was 79.1% vs 64.6% in Black patients and 89.4% vs 74.2% in White patients. The most common grade 3/4 TEAEs were neutropenia (D-VRd vs VRd: Black, 50.0% vs 22.2%; White, 47.0% vs 17.6%) and lymphopenia (Black, 28.6% vs 38.9%; White, 22.9% vs 16.2%). No deaths due to TEAEs were reported among Black patients in either arm, and 1 death due to pneumonia was reported among White patients in the D-VRd arm.
  • Chari et al (2024)9 reported the final efficacy and safety analysis results of clinically relevant subgroups from the GRIFFIN study. The MRD-negativity rates (10-5) were higher in the D-VRd arm vs the VRd arm in patients ≥65 years (67.9% vs 17.9%, respectively), with high-risk cytogenetic abnormalities ([HRCAs]; 54.8% vs 32.4%, respectively), and with gain/amp(1q21) (61.8% vs 28.6%, respectively). The hazard ratio (HR) point estimates for PFS favored the D-VRd vs VRd arm in patients ≥65 years (HR, 0.29; 95% CI, 0.06-1.48), with HRCAs (HR, 0.38; 95% CI, 0.14-1.01), and with gain/amp1(1q21) (HR, 0.42; 95% CI, 0.14-1.27). In patients aged ≥65 years, grade 3/4 TEAEs were reported in 88.9% vs 77.8% of patients in the D-VRd vs VRd arm. TEAEs leading to discontinuation of ≥1 treatment component were higher in D-VRd vs VRd, 37.0% vs 25.9% respectively.  
  • Callander et al (2024)10 reported post hoc analysis results evaluating the clinical efficacy of DARZALEX-based quadruplet therapies including DARZALEX + carfilzomib + lenalidomide + dexamethasone (D-KRd) and D-VRd in transplant-eligible patients with NDMM with HRCAs from the MASTER and GRIFFIN studies, respectively. In GRIFFIN, in patients with 0, 1 and ≥2 HRCAs, respectively, ≥CR was achieved by 90.9%, 78.8%, and 61.5%, the 24-month PFS rate was 96.7%, 93.8%, and 64.2%, and MRD-negativity (10-5) was reported in 76.1%, 55.9%, and 61.5%. In GRIFFIN, 1 patient with 1 HRCA and 4 patients with ≥2 HRCAs died of PD.
  • Sborov et al (2022)11 conducted a post hoc analysis to evaluate the risk and incidence of vascular thrombotic events (VTEs) in patients receiving D-VRd vs VRd in the GRIFFIN study. At a median follow-up of 38.6 months, VTEs were reported in 10.1% (n=10) of patients in the D-VRd arm and 15.7% (n=16) of patients in the VRd arm. The most common any-grade VTEs were deep vein thrombosis (D-VRd, 2.0%; VRd, 6.9%), pulmonary embolism (D-VRd, 2.0%; VRd, 3.9%), and embolism classified as unspecified vessel type and mixed arterial and venous (D-VRd, 2.0%; VRd, 2.9%). Among patients experiencing VTEs, clinical response deepened over time and response rates were higher in the D-VRd vs VRd arm after 2 years of maintenance.
  • Silbermann et al (2023)12 presented a post hoc analysis of the GRIFFIN study that evaluated patient-reported outcomes (PROs) during the maintenance therapy phase. During this phase, the proportion of patients reporting “not at all” or “a little” in the symptoms of hip pain increased from 69% to 85% from baseline to maintenance month 24 in the D-VRd/D-R arm and decreased from 83% to 78% in the VRd/R arm. Additionally, the proportion of patients reporting “not at all” or “a little” trouble taking a long walk increased from 61% to 85% from baseline to maintenance month 24 in the D-VRd/D-R arm and from 61% to 87% in the VRd/R arm.
  • Silbermann et al (2024)13 reported PROs from GRIFFIN at the final study analysis (median follow-up, 49.6 months) following ≥1 year of follow-up, death, or withdrawal from the study for all patients. In the D-VRd vs VRd group, a clinically meaningful improvement was observed after consolidation and maintenance in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-Item (EORTC QLQ-C30) global health status (GHS), physical functioning, and pain symptoms. A similar improvement was also observed in EuroQol 5-Dimension 5-Level (EQ-5D-5L) visual analog scale (VAS) scores and in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma Module 20-Item (EORTC QLQ-MY20) disease symptoms and future perspective scores. The median time to worsening of the EORTC QLQ-C30 GHS score was 30 months longer in the D-VRd vs VRd group.
  • Chhabra et al (2023)14 conducted a post hoc analysis evaluating the patient characteristics, stem cell mobilization and yields, and transplant outcomes after frontline DARZALEX-based induction therapy in the MASTER and GRIFFIN studies. In GRIFFIN, the median cluster of differentiation 34 positive (CD34+)cell yield in the D-VRd vs VRd arm was 8.3×106 cells/kg vs 9.4×106 cells/kg, respectively. For each regimen, a numerically higher stem cell yield was reported in patients who received upfront plerixafor vs those who received rescue plerixafor (D-VRd, 8.8×106 cells/kg vs 7.1×106 cells/kg, P=0.10; VRd, 10.5×106 cells/kg vs 9.4×106 cells/kg, P=0.20; respectively).12
  • Rodriguez-Otero et al (2025)15 reported results from a post hoc, pooled analysis of data from the PERSEUS and GRIFFIN studies. These studies evaluated the efficacy and safety of DARZALEX FASPRO and DARZALEX in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) vs VRd in patients aged ≥65 years. At a median follow-up of 47.5 months and 49.6 months, the median PFS was not reached in the PERSEUS and GRIFFIN groups, respectively. The PFS HR favored D-VRd vs VRd group (HR, 0.56; 95% CI, 0.31-1.01; P=0.05). The overall MRD-negativity rate (10-5) and sustained MRD-negativity rate (10-5) (≥12 months) in the D-VRd vs VRd group was 66.4% vs 41.7% and of 52.5% vs 26.1%, respectively. A higher incidence of grade 3/4 infections was observed in the D-VRd vs VRd group in patients aged ≥65 years (36.3% vs 24.8%, respectively). The percentage of TEAEs that resulted in the discontinuation of ≥1 study drug was similar between the D-VRd and VRd groups (40.8% and 45.6%, respectively) in patients aged ≥65 years.

PRODUCT LABELING

CLINICAL DATA

GRIFFIN (MMY2004; NCT02874742)1-3 was a 2-part, randomized, active-controlled, phase 2 United States (US) study that evaluated the safety and efficacy of D-VRd in patients with NDMM eligible for HDT and ASCT.

Study Design/Methods

  • Of note, the data presented utilized the abbreviation “RVd”, which has been replaced with “VRd” in the summary below to remain consistent throughout this scientific response.
  • Phase 2, randomized, open-label, active comparator-controlled, multicenter study.
  • The study enrolled 16 patients in the safety run-in phase, which assessed potential dose-limiting toxicities (DLTs) during cycle 1, and 207 patients in the randomized phase 2 portion.
  • DLTs were defined as reported adverse events (AEs) of:
    • Grade 4 neutropenia lasting >7 days
    • Grade 4 thrombocytopenia lasting >7 days despite transfusion support
    • Grade ≥3 nonhematological toxicity, except:
      • Grade 3 nausea, vomiting, or diarrhea that can be controlled within 48 hours with maximal supportive care
      • Grade 3 hyperglycemia that can be controlled within 48 hours with supportive care
      • Asymptomatic grade ≥3 electrolyte disturbances that can be controlled with repletion within 24 hours
      • Grade 3 maculopapular rash attributable to lenalidomide
    • Infusion-related reactions (IRRs):
      • Any grade 4 IRR occurring within 48 hours of infusion of DARZALEX
      • Any grade 3 IRR occurring within 48 hours of infusion of DARZALEX that does not resolve with a reduced infusion rate or temporarily stopping the infusion, as well as administration of supportive care and symptomatic therapy such as a steroid and an antihistamine
  • The safety run-in phase consisted of an induction phase (cycles 1-4; 21-day cycles), followed by ASCT, followed by a consolidation phase (cycles 5-6; 21-day cycles), that was initiated 60-100 days after ASCT, followed by a maintenance phase (cycles 7-32; 28-day cycles).
    • From the induction phase through the consolidation phase, patients received:
      • DARZALEX 16 mg/kg intravenously (IV) weekly in cycles 1-4 and every 3 weeks in cycles 5-6
      • Lenalidomide 25 mg orally (PO) on days 1-14
      • Bortezomib 1.3 mg/m2 subcutaneously (SC) on days 1, 4, 8, and 11
      • Dexamethasone 40 mg PO weekly (20 mg PO on days 1, 2, 8, 9, 15, and 16)
    • During the maintenance phase, patients received:
      • DARZALEX 16 mg/kg IV every 4 weeks or 8 weeks.
      • Lenalidomide 10 mg PO daily on days 1-21, then 15 mg PO daily beginning cycle 10 (if no tolerability issues)
      • Dexamethasone 20 mg PO every 8 weeks on days 1, 2, 8, 9, 15, and 16
    • One interim safety analysis was performed as planned for the safety run-in patients after treated for ≥4 cycles or discontinued study participation.
  • Following successful completion of the safety run-in phase, in part 2 of the study patients were randomized 1:1 to an induction phase (D-VRd or VRd [cycles 1-4; 21-day cycles]), followed by ASCT, followed by a consolidation phase (D-VRd or VRd [cycles 5-6; 21-day cycles]), followed by a maintenance phase (DARZALEX + lenalidomide or lenalidomide monotherapy [cycles 7-32; 28-day cycles]), following the dosing illustrated above, +/- DARZALEX.
  • A data review committee was established to review safety data after 8, 12, and 16 patients in the safety run-in phase completed cycle 1, and to determine if the study should proceed to the randomized phase 2 portion or stop.
  • Key inclusion criteria: age 18-70 years; documented MM per International Myeloma Working Group (IMWG) 2015 criteria; eligible for HDT/ASCT; Eastern Cooperative Oncology Group performance score of 0 to 2; adequate organ function; no prior systemic therapy for MM; measurable disease; creatinine clearance (CrCl) ≥30 mL/min
  • Primary objective: determine if the addition of DARZALEX to VRd will increase the sCR rate by the end of the post-ASCT consolidation therapy
  • Primary endpoints: sCR (by end of post-ASCT consolidation)
  • Secondary endpoints: MRD (10-5 via next-generation sequencing [NGS]), CR, overall response rate (ORR), ≥VGPR, duration of response (DOR), time to CR or sCR, PFS, and overall survival (OS)

Part 1: Safety Run-in Phase Final Analysis

Voorhees et al (2021)4 reported the final analysis of the safety run-in cohort of the GRIFFIN study.

Results

Baseline Characteristics
  • Demographics and baseline characteristics are presented in Table: Baseline Characteristics.
  • Median follow-up was 40.8 months (range, 20.6-43.0) after patients completed D-VRd treatment and 24 months of D-R maintenance therapy.
  • All patients in the safety run-in phase (N=16) completed induction therapy, stem cell mobilization, ASCT, consolidation, and entered maintenance therapy.
  • A total of 87.5% (n=14) of patients completed study therapy, and 2 (12.5%) discontinued the therapy because of PD (n=1) or AE (n=1; neuralgia or thrombocytopenia) during maintenance therapy.
  • Stem cell collection and neutrophil and platelet engraftment are present in Table: Stem Cell Collection and Transplantation.

Baseline Characteristics4
Characteristic
D-VRd (n=16)
Age, years
   Median (range)
62.5 (46-65)
      <65 years, n (%)
14 (87.5)
      ≥65 years, n (%)
2 (12.5)
Sex, n (%)
   Male
8 (50.0)
   Female
8 (50.0)
Race, n (%)
   White
11 (68.8)
   Black or African American
4 (25.0)
   Asian
1 (6.3)
ECOG PS, n (%)a
   0
3 (18.8)
   1
10 (62.5)
   2
3 (18.8)
ISS disease stage, n (%)b
   I
12 (75.0)
   II
2 (12.5)
   III
2 (12.5)
Cytogenetic risk profile, n (%)c
   Standard
12 (75.0)
   High risk
4 (25.0)
Median (range) time since diagnosis of MM, months
1.6 (0-5)
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; MM, multiple myeloma; t, translocation.
aECOG PS is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bISS disease stage is based on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease.
cCytogenetic risk was assessed by fluorescence in situ hybridization (locally tested); high risk was defined as the presence of del(17p), t(4;14), or t(14;16) in those patients with cytogenetic risk data available.

Stem Cell Collection and Transplantation4
Parameter
D-VRd (n=16)
Median (range) CD34+ yield, ×106 cells/kg
8.05 (3.5-17.6)
Median (range) CD34+ cells transplanted, ×106 cells/kg
4.72 (2.2-6.0)
Patients receiving plerixafor for mobilization, n (%)
9 (56.3)
Patients receiving cyclophosphamide, n (%)
0
Median (maximum) days to neutrophil (0.5×109/L) engraftment,a
14
Median (maximum) days to platelet (20×109/L) engraftment,b
13.5
Abbreviations: CD34+,cluster of differentiation 34 positive; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone.
aFor neutrophil engraftment, there were 15 evaluable patients.
bFor platelet engraftment, there were 16 evaluable patients.
Safety
  • During cycle 1, 3 of 16 patients developed 4 DLTs: fatigue, gastroenteritis, hypotension, and pneumonitis. All DLTs were grade 3 and none resulted in treatment discontinuation during induction or consolidation therapy.
  • One patient had a TEAE leading to discontinuation of study treatment.
  • Fourteen (87.5%) patients experienced any-grade infections and 5 (31.3%) patients experienced grade 3/4 infections.
    • During the maintenance phase, 31.3% (n=5) of patients experienced any-grade infections, the most common being upper respiratory tract infections. One (6.3%) patient experienced a grade 3/4 infection (pneumonia and bronchitis).
  • Grade 1/2 IRRs occurred in 31.3% (n=5) of patients. IRRs included pruritus, chills, flushing, maculo-papular rash, and vascular access site swelling; all occurred during cycle 1 except vascular access site swelling.
  • Eleven (68%) patients experienced a serious AE. For the incidences of grade 3/4 TEAEs, please see Table: Most Common Grade 3/4 TEAEs.

Most Common Grade 3/4 TEAEs4
Events, n (%)
D-VRd (n=16)
Grade 3/4a
Total
15 (93.8)
Most commonly occurring
   Neutropenia
7 (43.8)
   Pneumonia
5 (31.3)
   Lymphopenia
5 (31.3)
   Thrombocytopenia
4 (25.0)
   Hypertension
3 (18.8)
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone, TEAE, treatment-emergent adverse event.
aNo grade 5 TEAEs were reported.
Efficacy
  • At a median follow-up of 40.8 months (range, 20.6-43.0), disease progression occurred in 3 patients.
  • Median time to first response was 0.77 months (range, 0.1-2.1), and median DOR was not estimable.
  • Median time to ≥CR was 7.36 months (range, 2.8-18.5), and median duration of ≥CR was not estimable.
  • Estimated 24-months PFS and OS rates was 93.8%.
  • Estimated 36-month PFS and OS rates were 78.1% and 93.8%, respectively.
  • MRD-negativity rates at 10-5 sensitivity threshold and 10-6 sensitivity threshold, respectively:
    • By end of D-VRd induction: 18.8% (n=3) vs 0%.
    • By end of D-VRd consolidation: 50% (n=8) vs 0%.
    • At the last follow-up: 81.3% (n=13) vs 31.3% (n=5)
  • MRD-negativity rates of 10-5 were sustained for ≥12 months in 8 (50.0%) patients.
  • Response rates are presented in Table: Updated Response Rates Over Time for the Safety Run-in Cohort.

Updated Response Rates Over Time for the Safety Run-in Cohorta,4
Patients, %
By End of
D-VRd Induction
By End of
D-VRd Consolidation
By Last Follow-up
D-R Maintenance
sCR
-
56.3
93.8
CR
12.5
12.5
-
≥CR
12.5
68.8
93.8
VGPR
56.3
31.3
6.3
PR
31.3
-
-
Abbreviations: CR, complete response; ≥CR, complete response or better; D-R, DARZALEX + lenalidomide; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
Response data are shown for the response-evaluable population (N=16).
aPercentages do not add up to 100% due to rounding.

Part 2: Randomized Phase

Voorhees et al (2020)2,3,16 presented the primary analysis and updated analysis of the randomized portion of this study. Kaufman et al (2020)17 presented a 1-year update of the safety and efficacy results at the 62nd ASH Annual Meeting & Exposition in December 2020. Laubach et al (2021)5 presented updated efficacy and safety results after 2 years of maintenance therapy in the GRIFFIN study. Voorhees et al (2023)6 reported the final efficacy and safety results after all patients completed ≥1 year of follow-up after the end-of-study treatment, died, or withdrew from study participation.

Results

Baseline Characteristics
  • A total of 207 patients were randomized (D-VRd, n=104; VRd, n=103).
  • The median follow-up was 13.5 months in the primary analysis and 22.1 months in the updated analysis.
  • Ninety percent of patients in the D-VRd arm underwent ASCT compared to 76% in the VRd arm (ASCT rate lower due to early discontinuations).
  • Baseline patient characteristics are summarized in Table: Patient Demographics in the Randomized Phase (ITT).

Patient Demographics in the Randomized Phase (ITT)3
Characteristic
D-VRd (n=104)
VRd (n=103)
Age
   Median (range), years
59 (29-70)
61 (40-70)
   ≥65 years
28 (26.9)
28 (27.2)
Male, n (%)
58 (55.8)
60 (58.3)
ECOG PS,a n (%)
n=101
n=102
   0
39 (38.6)
40 (39.2)
   1
51 (50.5)
52 (51)
   2
11 (10.9)
10 (9.8)
ISS stage,b n (%)
   I
49 (47.1)
50 (48.5)
   II
40 (38.5)
37 (35.9)
   III
14 (13.5)
14 (13.6)
Baseline CrCl, n (%)
  30-50 mL/minute
9 (8.7)
9 (8.7)
   >50 mL/minute
95 (91.3)
94 (91.3)
Cytogenetic profile,c n (%)
n=98
n=97
   Standard risk
82 (83.7)
83 (85.6)
   High risk
16 (16.3)
14 (14.4)
Time since diagnosis of MM
n=103
n=102
   Median (range), months
0.7 (0-12)
0.9 (0-61)
Abbreviations: CrCl, creatinine clearance; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; ITT, intent-to-treat; MM, multiple myeloma; VRd, bortezomib + lenalidomide + dexamethasone.
aECOG PS is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bISS disease stage is based on the combination of serum-β2-microglobulin and albumin levels. Higher stages indicate more advanced disease.
cCytogenetic risk was assessed by fluorescence in situ hybridization, high risk was defined as the presence of del17p, t(4:14), or t(14:16) among patients with available cytogenetic risk data.
Efficacy
  • The primary endpoint was met with D-VRd improving the sCR rate by end of consolidation (D-VRd vs VRd: 42.4% vs 32.0%; OR, 1.57; 95% CI, 0.87-2.82; 1-sided P=0.068). The study had 80% power to detect a 15% improvement with a 1-sided alpha of 0.1.
  • A significantly higher proportion of patients achieved an ORR following consolidation in the D-VRd arm vs the VRd arm (99.0% vs 91.8%; 2-sided P=0.0160).
  • The rate of ≥VGPR was 90.9% with D-VRd vs 73.2% with VRd.
  • The rate of ≥CR was 51.5% with D-VRd vs 42.3% with VRd.
  • The percentage of patients achieving ≥CR at the end of induction, ASCT, consolidation, and clinical cutoff in the D-VRd arm was 19.2%, 27.3%, 51.5%, and 79.8%, respectively, vs 13.4%, 19.6%, 42.3%, and 60.8% in the VRd arm.
  • MRD (10-5 via NGS) among patients achieving ≥CR greater with D-VRd vs VRd: 58.8% vs 24.4% (OR, 4.65; 95% CI, 1.76-12.28; P=0.0014).
  • In the intent-to-treat (ITT) population, 51% of patients in the D-VRd arm achieved post-ASCT MRD-negativity vs 20.4% of patients in the VRd arm, regardless of response (OR, 4.70; 95% CI, 2.38-9.28; P<0.0001). Additional MRD results are presented in Table: Post-consolidation MRD-Negativity.
  • Median stem cell yield (D-VRd vs VRd): 8.2 vs 9.4×106 cells

Post-consolidation MRD-Negativity3
MRD-Negative Status (10-5),a n (%); ITT
D-VRd (n=104)
VRd (n=103)
OR (95% CI)b
P valuec
MRD negative regardless of response
53/104 (51.0)
21/103 (20.4)
4.07 (2.18-7.59)
<0.0001
MRD negative with CR or better
49/104 (47.1)
19/103 (18.4)
3.89 (2.07-7.33)
<0.0001
In patients achieving CR or better
49/69 (62.0)
19/59 (32.2)
3.57 (1.72-7.44)
0.0006
MRD-evaluable population
53/77 (68.8)
21/65 (32.3)
4.47 (2.19-9.11)
<0.0001
Abbreviations: CI, confidence interval; CR, complete response; CrCl, creatinine clearance; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NGS, next-generation sequencing; OR, odds ratio; VRd, bortezomib + lenalidomide + dexamethasone.
aThe threshold of MRD-negativity was defined as 1 tumor cell per 105 white cells. MRD status is based on assessment of bone marrow aspirates by NGS in accordance with International Myeloma Working Group criteria. MRD assessments occurred in patients who had both baseline (with clone identified/calibrated) and postbaseline MRD (with negative, positive, or indeterminate result) samples taken (D-VRd, n=71; VRd, n=55). Patients with a missing or inconclusive assessment were considered MRD positive.
bMantel-Haenszel estimate of the common OR for stratified tables is used. The stratification factors are ISS stage (I, II, III) and CrCl (30-50 mL/min or >50 mL/min) at randomization. An OR >1 indicates an advantage for the DARZALEX group.
cP values were calculated from the Fisher’s exact test.
  • At the median follow-up of 22.1 months, D-VRd achieved higher sCR (62.6% vs 45.4%; OR, 1.98; 95% CI, 1.12-3.49; 2-sided P=0.0177), CR (17.2% vs 15.5%), and ≥CR (79.8% vs 60.8%; OR, 2.53; 95% CI, 1.33-4.81; 2-sided P=0.0045) vs VRd.
  • In the ITT population, median PFS and OS were not reached (NR) in the D-VRd and VRd arms. In the D-VRd and VRd arms, respectively (Kaplan-Meier estimates):
    • 12-month PFS rates were 96.9% and 95.3%.
    • 24-month PFS rates were 95.8% and 89.8%.
    • 12-month OS rates were 99.0% and 97.9%.
    • 24-month OS rates were 95.8% and 93.4%.
  • DARZALEX did not impact time to engraftment and hematopoietic reconstitution (Table: Stem Cell Collection and Transplantation).

Stem Cell Collection and Transplantation16
Parameter
D-VRd
VRd
Median (range) stem cell yield, ×106 CD34+ cells/kga,b
8.2 (3-33)
9.4 (4-29)
Median stem cells transplanted, ×106 CD34+ cells/kgc
4.2
4.8
Patients receiving plerixafor for mobilization, n (%)d
66 (70)
45 (56)
Patients receiving cyclophosphamide, n (%)d
5 (5)
4 (5)
Median (max) days to neutrophil engraftment (0.5×109/L)
12 (31)
12 (23)
Median (max) days to platelet engraftment (20×109/L)
13 (31)
12 (23)
Abbreviations: CD34+,cluster of differentiation 34 positive; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; G-CSF, granulocyte colony-stimulating factor; max, maximum; VRd, bortezomib + lenalidomide + dexamethasone.
aAmong patients who underwent peripheral blood stem cell apheresis (D-VRd, n=93; VRd, n=80).
bOne patient in the D-VRd arm had a stem cell yield <3×106 cells/kg; no patients in either arm had a stem cell yield <2×106 cells/kg.
cAmong patients receiving transplant (D-VRd, n=94; VRd, n=78).
dAmong patients who underwent mobilization (D-VRd, n=95; VRd, n=80). Patients underwent stem cell mobilization with G-CSF with or without plerixafor, according to institutional standards; if unsuccessful, cyclophosphamide-based mobilization was permitted.
Safety
  • In the updated safety and efficacy analysis, any-grade infections occurred in 91% of patients in the D-VRd arm and 62% of patients in the VRd arm, the most common being grade 1/2 upper respiratory tract infections; grade 3/4 infections were seen in 23% of patients in the D-VRd arm vs 22% of patients in the VRd arm.
  • Pneumonia was reported in 13% of patients in the D-VRd arm and 15% of patients in the VRd arm.
  • TEAEs are summarized in Table: Most Common TEAEs.

Most Common TEAEsa,3,16
TEAEs, n (%)
D-VRd (n=99)
VRd (n=102)
Any-Grade
Grade 3/4
Any-Grade
Grade 3/4
Hematologic
   Neutropenia
57 (57.6)
41 (41.4)
36 (35.3)
22 (21.6)
   Thrombocytopenia
43 (43.4)
16 (16.2)
36 (35.3)
9 (8.8)
   Leukopenia
36 (36.4)
16 (16.2)
29 (28.4)
7 (6.9)
   Anemia
35 (35.4)
9 (9.1)
33 (32.4)
6 (5.9)
   Lymphopenia
30 (30.3)
23 (23.2)
28 (27.5)
22 (21.6)
Nonhematologic
   Fatigue
68 (68.7)
6 (6.1)
62 (60.8)
6 (5.9)
   Upper respiratory tract infection
62 (62.6)
1 (1.0)
45 (44.1)
2 (2.0)
   Peripheral neuropathyb
59 (59.6)
7 (7.1)
74 (72.5)
8 (7.8)
   Diarrhea
59 (59.6)
7 (7.1)
51 (50.0)
4 (3.9)
   Constipation
51 (51.5)
2 (2.0)
40 (39.2)
1 (1.0)
   Cough
50 (50.5)
0
27 (26.5)
0
   Nausea
49 (49.5)
2 (2.0)
50 (49.0)
1 (1.0)
   Pyrexia
45 (45.5)
2 (2.0)
28 (27.5)
3 (2.9)
   Insomnia
42 (42.4)
2 (2.0)
31 (30.4)
1 (1.0)
   Back pain
36 (36.4)
1 (1.0)
34 (33.3)
4 (3.9)
   Edema peripheral
34 (34.3)
2 (2.0)
35 (34.3)
3 (2.9)
   Arthralgia
33 (33.3)
0
33 (32.4)
2 (2.0)
IRRs
42 (42.4)
6 (6)c
-
-
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; IRR, infusion-related reaction; TEAE, treatment-emergent adverse event; VRd, bortezomib + lenalidomide + dexamethasone.
aAny-grade TEAEs are listed that occurred in ≥30% of patients in either arm. The safety analysis population included all randomized patients who received ≥1 dose of study treatment; analysis was according to treatment received.
bIncludes patients with neuropathy peripheral and peripheral sensory neuropathy.
cNo grade 4 IRRs were reported.

Final Efficacy and Safety Analysis of Maintenance Therapy

Voorhees et al (2023)6 reported the final efficacy and safety results after all patients completed ≥1 year of follow-up after the end-of-study treatment, died, or withdrew from study participation.

Results

Patient Characteristics
  • At the time of the final analysis, all patients completed ≥1 year of follow-up after the end-of-study treatment, died, or withdrew from the study.
  • The median duration of follow-up was 49.6 months (interquartile range [IQR], 47.4-52.1).
  • By the final analysis, 25% of patients in the D-VRd arm and 51% in the VRd arm discontinued treatment. See Table: Patient Disposition.
  • The median duration of treatment in the D-VRd and VRd arms was 32.5 months (IQR, 31.1-33.4) and 27.5 months (IQR, 2.9-32.7), respectively.
    • In the D-VRd arm, among the 90 patients who received DARZALEX and lenalidomide maintenance therapy, 21% (n=19) switched from DARZALEX to DARZALEX FASPRO and received ≥1 cycle of DARZALEX FASPRO (median number, 3.0 [IQR, 3.0-5.0]).

Patient Disposition6
Patients, n
D-VRd (n=104)
VRd (n=103)
Treated with maintenance therapy
90
70
Completed maintenance therapy
74
48
Discontinued treatment during maintenance therapy
16
22
   AE
6
7
   PD
3
8
   Patient withdrawal
2
4
   Lost to follow-up
2
0
   Death
1
1
   Other
2
2
Discontinued treatment by final analysis
26
53
Abbreviations: AE, adverse event; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; PD, progressive disease; VRd, bortezomib + lenalidomide + dexamethasone.
Efficacy
  • At the final analysis, among response-evaluable patients in the D-VRd (n=100) vs VRd (n=98) arm, respectively, sCR was achieved in 67% vs 48% of patients (OR, 2.18; 95% CI, 1.22-3.89; 2-sided P=0.0079) and ≥CR in 83% vs 60% of patients (P=0.0005). Response data over time are summarized in Table: Summary of Response Over Time.6,18

Summary of Response Over Time6
Timepoint, %
D-VRd
VRd
sCR
CR
≥CR
VGPR
PR
SD/PD/
NE
sCR
CR
≥CR
VGPR
PR
SD/PD/
NE
End of inductiona
12
7
19
53
26
2
7
6
13
43
35
8
End of post-ASCT consolidationa
42
9
52
39
8
1
32
10
42
31
19
8
Final analysisb
67
16
83
13
3
1
48
12
60
17
14
8
Abbreviations: ASCT, autologous stem cell transplant; CR, complete response; ≥CR, complete response or better; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; NE, not evaluable; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.
Rates shown are the number of patients with each type of response divided by the response-evaluable population.aResponse rates were from the primary analysis cutoff (median follow-up, 13.5 months) and the response-evaluable population comprised 196 patients (D-VRd, n=99; VRd, n=97).
bResponse rates were also evaluated at the time of the final analysis (median follow-up 49·6 months; IQR 47.4-52·1), and the response-evaluable population comprised 198 patients (D-VRd, n=100; VRd, n=98).

Response Duration Among Patients in the D-VRd vs VRd Arm6
Parameter
D-VRd
VRd
Median duration to first response (ORR), months (95% CI)
0.8 (0.8-0.8)
0.8 (0.8-1.0)
Median duration to sCR, months (95% CI)
10.2 (8.8-13.0)
14.3 (9.2-21.7)
   HR (95% CI)
1.26 (0.86-1.83)
   P value
0.2339
Median duration to ≥VGPR, months (95% CI)
2.2 (2.1-2.7)
3.0 (2.2-6.3)
Median duration to ≥CR, months (95% CI)
8.9 (7.9-9.4)
9.6 (8.4-12.2)
Median DOR
NR
NR
   Estimated 48-month DOR, % (95% CI)
89 (79.9-94.3)
71 (55.8-81.4)
Abbreviations: CI, confidence interval; ≥CR, complete response or better; DOR, duration of response; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; HR, hazard ratio; NR, not reached; ORR, overall response rate; sCR, stringent complete response; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.

Final Analysis of Best Response and MRD-Negativity Rates at the End of Maintenance6,18
Parameter
D-VRd
VRd
P value
Response,a n
100
98
-
   ORR, n (%)
99 (99)
90 (92)
0.016b
      ≥CR
83 (83)
59 (60)
0.0005b
      CR
16 (16)
12 (12)
-
      sCR
67 (67)
47 (48)
0.0079b
      ≥VGPR
96 (96)
76 (78)
0.0002b
      VGPR
13 (13)
17 (17)
-
      PR
3 (3)
14 (14)
-
   SD, n (%)
1 (1)
8 (8)
-
   PD, n (%)
0
0
-
MRD negative
   ITT population, n
104
103
-
      10-5 sensitivity, n (%)
67 (64)
31 (30)
<0.0001c
         OR (95% CI)
4.23 (2.35-7.62)
      10-6 sensitivity, n (%)
37 (36)
16 (16)
0.0013c
         OR (95% CI)
2.95 (1.52-5.75)
   In patients achieving ≥CR, n
83
59
-
      10-5 sensitivity, n (%)
64 (77)
28 (47)
0.0004c
      10-6 sensitivity, n (%)
35 (42)
14 (24)
0.031c
Durable MRD negativity
   Lasting ≥12 months, n
104
103
-
      10-5 sensitivity, n (%)
46 (44)
14 (14)
<0.0001c
         OR (95% CI)
5.00 (2.50-9.99)
      10-6 sensitivity, n (%)
10 (10)
4 (4)
0.16c
         OR (95% CI)
2.48 (0.76-8.07)
Abbreviations: CI, confidence interval; CR, complete response; ≥CR, complete response or better; CrCl, creatinine clearance; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ISS, International Staging System; ITT, intent-to-treat; MM, multiple myeloma; MRD, minimal residual disease; NGS, next-generation sequencing; OR, odds ratio; ORR, overall response rate; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.
The predefined per protocol final analysis occurred after all patients completed ≥1 year of long-term follow-up after the end-of-study treatment, died, or withdrew from study participation, whichever occurred first.
aResponse rate is based on the response-evaluable population, which included randomized patients who had a confirmed diagnosis of MM, had measurable disease at baseline, received ≥1 dose of study treatment, and had ≥1 postbaseline disease assessment. The response-evaluable population for the primary analysis included 99 patients in the D-VRd group and 97 patients in the VRd group.
bP value was calculated using the Cochran-Mantel-Haenszel Chi-square test stratified by ISS disease stage (I, II, or III) and baseline CrCl (30-50 mL/min or >50 mL/min) at randomization.
cP value was calculated using Fisher’s exact test.
  • By the end of the 2-year maintenance therapy, 14% (n/N=15/104) and 10% (n/N=10/103) of patients in the D-VRd and VRd arms, respectively, who were previously MRD positive at the end of the consolidation phase, converted to MRD negative (10-5). MRD-negativity rates continuously improved over time and were consistently higher in the D-VRd vs VRd arm. See Table: Summary of MRD-Negativity Rates Over Time (ITT Population).

Summary of MRD-Negativity Rates Over Time (ITT Population)a, 6,18
Timepoint, %
D-VRd
VRd
MRD-Negativity (10-5)
MRD-Negativity (10-6)
MRD-Negativity (10-5)
MRD-Negativity (10-6)
End of induction
22
1
8
0
Post-ASCT consolidation
50
11
20
3
End of study
64
36
30
16
Abbreviations: ASCT, autologous stem cell transplant; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ITT, intent-to-treat; MRD, minimal residual disease; VRd, bortezomib + lenalidomide + dexamethasone. aMRD was evaluated by NGS using the clonoSEQ assay. MRD assessments occurred at the first evidence of suspected CR or sCR, after induction (but before stem cell collection), after consolidation, and after 12 and 24 months of maintenance, regardless of response.
  • No patient in either treatment arm with sustained MRD-negativity 10-5 lasting ≥12 months became MRD positive later.
  • The median time to MRD-negativity in the D-VRd vs VRd arm at sensitivity thresholds of 10-5 and 10-6, respectively, was 8.5 vs 34.6 months (HR, 2.70; 95% CI, 1.72-4.23; P<0.0001) and 33.9 months vs NR (HR, 1.93; 95% CI, 1.05-3.54; P=0.031).
  • Efficacy and survival outcomes are summarized in Table: Efficacy and Survival Outcomes (ITT Population).

Efficacy and Survival Outcomes (ITT Population)6,18
Parameter
D-VRd
VRd
Median PFS, months
NR
NR
   3-year PFS rate, %
89
80.7
   4-year PFS rate, %
87.2
70
   PFS HR (95% CI); P value
0.45 (0.21-0.95); 0.032
Median PFS in patients who received lenalidomide therapy as per SoC after study completion, months
NR
NR
4-year PFS rate in patients who received SoC lenalidomide therapy after study completion, %
96
80
Median PFS in patients who did not receive lenalidomide therapy as per SoC after study completion, months
NR
NR
4-year PFS rate in patients who did not receive SoC lenalidomide therapy after study completion, %
100
86
Median OS, months
NR
NR
   3-year OS rate, %
92.7
92.2
   4-year OS rate, %
92.7
92.2
   OS HR (95% CI); P value
0.90 (0.31-2.56); 0.84a
Disease progression or death, n/N (%)
11/104 (11)
18/103 (17)
   HR (95% CI)
0.45 (0.21-0.95)
   P value
0.032
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; HR, hazard ratio; ISS, International Staging System; ITT, intention-to-treat; NR, not reached; OS, overall survival; PFS, progression-free survival; SoC, standard of care; VRd, bortezomib + lenalidomide + dexamethasone.
aHR and 95% CI are from a Cox proportional hazards model with treatment as the sole explanatory variable and stratified with ISS staging (I, II, and III) and baseline CrCl (30-50 mL/min or >50 mL/min) at randomization.
An HR <1 indicates an advantage for D-VRd. P value is based on the log-rank test stratified with ISS staging and baseline CrCl at randomization.
Safety
  • Among safety-evaluable patients in the D-VRd (n=99) vs VRd (n=102) arms, grade 3/4 TEAEs occurred in 86% (n=85) vs 79% (n=81), respectively.
  • In the D-VRd vs VRd arm, serious TEAEs occurred in 46% (n=46) vs 52% (n=53) of patients, respectively.
    • The most common serious TEAEs included pneumonia (15% vs 14%) and pyrexia (11% vs 10%).
  • TEAEs leading to treatment discontinuation were similar across treatment arms (D-VRd, 33% [n=33]; VRd, 31% [n=32]). One patient in each arm died due to TEAEs unrelated to study treatment.
  • Any-grade infections were more common in the D-VRd vs VRd arm (93% [n=92] vs 66% [n=67]). Similar incidence rates were reported across treatment arms for grade 3/4 infections (D-VRd, 29%; VRd, 26%) and infections leading to treatment discontinuation (D-VRd, 2%; VRd, 3%).
    • During maintenance therapy (cycle 7 and onwards) in the D-VRd vs VRd arm, any-grade infections occurred in 35% (n/N=31/89) vs 32% (n/N=23/71) of patients and grade 3/4 infections occurred in 18% (n=16) vs 21% (n=15) of patients.
    • In the D-VRd vs VRd arm, Coronavirus Disease 2019 (COVID-19) infections were reported in 5% (n=5) vs 2% (n=2) of patients, respectively. Of these, 1 patient in each arm had a grade 3 COVID-19-related event (including 1 serious event in the D-VRd arm).
  • TEAEs occurring in the safety population are summarized in Table: Most Common TEAEs in the Safety Population.
  • During maintenance therapy, second primary malignancies with first onset after the start of maintenance therapy were reported in 4% (n/N=4/89) evaluable patients in the D-VRd arm and 4% (n/N=3/71) evaluable patients in the VRd arm.
  • A total of 14 (D-VRd, n=7; VRd, n=7) patients died, of whom 9 (D-VRd, n=5; VRd, n=4) patients died due to PD.
  • There were 39% (n=39) IRRs reported at the initial infusion, 2% (n=2) IRRs at the second infusion, and 14% (n=14) IRRs at the subsequent infusions.18

Most Common TEAEs in the Safety Populationa,6,18
TEAEs, n (%)
D-VRd (n=99)
VRd (n=102)
Grade 1/2
Grade 3
Grade 4
Grade 1/2
Grade 3
Grade 4
Hematologic
   Anemia
28 (28)
9 (9)
0
27 (26)
5 (5)
1 (1)
   Thrombocytopenia
28 (28)
4 (4)
12 (12)
27 (26)
4 (4)
5 (5)
   Leukopenia
22 (22)
8 (8)
9 (9)
22 (22)
6 (6)
2 (2)
   Neutropenia
17 (17)
32 (32)
14 (14)
18 (18)
21 (21)
2 (2)
   Lymphopenia
8 (8)
13 (13)
10 (10)
6 (6)
20 (20)
3 (3)
Nonhematologic
   Hypokalemia
24 (24)
3 (3)
1 (1)
24 (24)
3 (3)
0
   Hypocalcemia
17 (17)
0
0
12 (12)
2 (2)
1 (1)
   Pneumoniab
11 (11)
11 (11)
1 (1)
4 (4)
14 (14)
0
   Hyperkalemia
6 (6)
1 (1)
0
1 (1)
0
1 (1)
   Cellulitis
6 (6)
0
1 (1)
3 (3)
1 (1)
0
   Hypophosphatemia
5 (5)
9 (9)
1 (1)
6 (6)
11 (11)
0
   Hyperuricemia
4 (4)
0
0
6 (6)
0
1 (1)
   Acute kidney injury
2 (2)
2 (2)
2 (2)
4 (4)
3 (3)
0
   Atrial fibrillation
1 (1)
0
1 (1)
3 (3)
0
0
   Increased blood creatine phosphokinase
1 (1)
0
0
0
0
1 (1)
   Atrial tachycardia
1 (1)
0
0
0
0
1 (1)
   Sepsis
0
1 (1)
2 (2)
0
1 (1)
0
   Drug reaction with eosinophilia and systemic symptoms
0
0
0
0
1 (1)
1 (1)
   Septic shock
0
0
0
0
0
1 (1)
   Cerebrovascular accident
0
0
0
0
0
1 (1)
   Systemic inflammatory
   response syndrome
0
0
0
0
0
1 (1)
   Death
0
0
0
0
0
0
IRRsc
49 (49)
7 (7)
0
-
-
-
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; IRR, infusion-related reaction; TEAE, treatment-emergent adverse event; VRd, bortezomib + lenalidomide + dexamethasone.
aThe maximum intensity for each preferred term is listed, and TEAEs are listed for all grade 4 or 5 events and any grade 3 events occurring in ≥10% of patients in either treatment arm (corresponding grade 1-2 events are listed).
bOne grade 5 event was recorded in the D-VRd group.
cThere were no grade 4/5 IRRs. Data pertaining to IRRs are not available for the VRd arm.

Post Hoc Analysis of Sustained MRD-Negativity

Rodriguez et al (2022)7 presented a post hoc analysis of the GRIFFIN study that assessed the sustained MRD-negativity (lasting ≥6 or ≥12 months) in clinically relevant subgroups as well as among patients with ≥CR.

Study Design/Methods

  • Sustained MRD-negativity (≥2 MRD-negative results in the bone marrow ≥6 or ≥12 months apart without any positive result in between) was evaluated in the ITT population.
  • This post hoc analysis included all patients who completed 2 years of maintenance therapy or discontinued treatment.

Results

Patient Characteristics

Demographics and Baseline Disease Characteristics Based on Duration of MRD-Negativity (10-5) in the ITT Population7
Characteristic
D-VRd
VRd
ITT
(n=104)
MRD-Negative
(10-5) Patients
ITT
(n=103)
MRD-Negative
(10-5) Patients
≥6 mo
(n=50)
≥12 mo
(n=46)
≥6 mo
(n=15)
≥12 mo
(n=13)
Median age (range), years
59 (29-70)
60 (29-70)
60 (29-70)
61 (40-70)
57 (40-68)
58 (40-68)
   <65 years, n (%)
76 (73)
34 (68)
32 (70)
75 (73)
12 (80)
10 (77)
   ≥65 years, n (%)
28 (27)
16 (32)
14 (30)
28 (27)
3 (20)
3 (23)
Sex, n (%)
   Male
58 (56)
26 (52)
24 (52)
60 (58)
8 (53)
7 (54)
   Female
46 (44)
24 (48)
22 (48)
43 (42)
7 (47)
6 (46)
Race, n (%)
n=103
n=50
n=46
n=103
n=15
n=13
   White
85 (83)
43 (86)
39 (85)
76 (74)
13 (87)
11 (85)
   Black or African American
14 (14)
6 (12)
6 (13)
18 (17)
1 (7)
1 (8)
   Asian
0
0
0
2 (2)
0
0
   Other/multiple/unknown
4 (4)
1 (2)
1 (2)
7 (7)
1 (7)
1 (8)
ECOG PS, n (%)a
n=101
n=50
n=46
n=102
n=15
n=13
   0
39 (39)
20 (40)
20 (43)
40 (39)
5 (33)
5 (38)
   1
51 (50)
23 (46)
19 (41)
52 (51)
8 (53)
6 (46)
   2
11 (11)
7 (14)
7 (15)
10 (10)
2 (13)
2 (15)
ISS disease stage, n (%)b
   I
49 (47)
23 (46)
20 (43)
50 (49)
5 (33)
3 (23)
   II
40 (38)
20 (40)
20 (43)
37 (36)
8 (53)
8 (62)
   III
14 (13)
7 (14)
6 (13)
14 (14)
2 (13)
2 (15)
   Missing
1 (1)
0
0
2 (2)
0
0
Cytogenetic profile, n (%)c
n=98
n=48
n=45
n=97
n=15
n=13
   Standard risk
82 (84)
44 (92)
42 (93)
83 (86)
13 (87)
11 (85)
   High risk
16 (16)
4 (8)
3 (7)
14 (14)
2 (13)
2 (15)
Revised cytogenetic profile, n (%)c
n=98
n=48
n=45
n=97
n=15
n=13
   Standard risk
56 (57)
33 (69)
31 (69)
60 (62)
8 (53)
7 (54)
   High risk
42 (43)
15 (31)
14 (31)
37 (38)
7 (47)
6 (46)
      gain 1q
34 (35)
14 (29)
13 (29)
28 (29)
5 (33)
4 (31)
      t(14;20)
1 (1)
0
0
1 (1)
0
0
Abbreviations: del, deletion; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; ITT, intent-to-treat; mo, months; MRD, minimal residual disease; t, translocation; VRd, bortezomib + lenalidomide + dexamethasone.
aECOG PS is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bISS disease stage is based on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease.
cCytogenetic risk was assessed by fluorescence in situ hybridization (local testing); high risk was defined as the presence of del17p, t(4;14), or t(14;16) among patients with available cytogenetic risk data, while revised high risk was defined as the presence of del17p, t(4;14), t(14;16), t(14;20), or gain 1q (≥3 copies of chromosome 1q21) among those patients.
Sustained MRD-Negativity

Subgroup Analysis of Rates of Sustained MRD-Negativity Lasting ≥6 Months at the 10-5 or 10-6 Sensitivity Thresholds7
Parameter
MRD-Negativity Lasting ≥6 Months, n/N (%)
Sensitivity Threshold of 10-5
Sensitivity Threshold of 10-6
D-VRd
VRd
D-VRd
VRd
ITT (overall)
50/104 (48.1)
15/103 (14.6)
17/104 (16.3)
5/103 (4.9)
   OR (95% CI)
5.18 (2.64-10.17)
3.66 (1.30-10.32)
Age
   <65 years
34/76 (44.7)
12/75 (16.0)
11/76 (14.5)
3/75 (4.0)
   OR (95% CI)
4.25 (1.98-9.14)
4.06 (1.09-15.20)
   ≥65 years
16/28 (57.1)
3/28 (10.7)
6/28 (21.4)
2/28 (7.1)
   OR (95% CI)
11.11 (2.71-45.61)
3.55 (0.65-19.37)
ISS disease stage
   I
23/49 (46.9)
5/50 (10.0)
6/49 (12.2)
1/50 (2.0)
   OR (95% CI)
7.96 (2.70-23.47)
6.84 (0.79-59.06)
   II
20/40 (50.0)
8/37 (21.6)
9/40 (22.5)
2/37 (5.4)
   OR (95% CI)
3.63 (1.34-9.84)
5.08 (1.02-25.33)
   III
7/14 (50.0)
2/14 (14.3)
2/14 (14.3)
2/14 (14.3)
   OR (95% CI)
6.00 (0.97-37.30)
1.00 (0.12-8.31)
Cytogenetic riska
   High
4/16 (25.0)
2/14 (14.3)
0/16
0/14
   OR (95% CI)
2.00 (0.31-13.06)
NE (NE-NE)
   Standard
44/82 (53.7)
13/83 (15.7)
17/82 (20.7)
5/83 (6.0)
   OR (95% CI)
6.23 (2.99-12.99)
4.08 (1.43-11.66)
Revised cytogenetic riska
   High
15/42 (35.7)
7/37 (18.9)
5/42 (11.9)
3/37 (8.1)
   OR (95% CI)
2.38 (0.84-6.72)
1.53 (0.34-6.90)
   Standard
33/56 (58.9)
8/60 (13.3)
12/56 (21.4)
2/60 (3.3)
   OR (95% CI)
9.33 (3.73-23.29)
7.91 (1.68-37.17)
Gain 1qa
14/34 (41.2)
5/28 (17.9)
5/34 (14.7)
3/28 (10.7)
   OR (95% CI)
3.22 (0.99-10.52)
1.44 (0.31-6.62)
≥CR
48/82 (58.5)
14/59 (23.7)
17/82 (20.7)
5/59 (8.5)
   OR (95% CI)
4.54 (2.16-9.54)
2.82 (0.98-8.16)
sCR
43/66 (65.2)
10/46 (21.7)
16/66 (24.2)
5/46 (10.9)
   OR (95% CI)
6.73 (2.84-15.98)
2.62 (0.89-7.77)
Abbreviations: CI, confidence interval; ≥CR, complete response or better; del, deletion; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; sCR, stringent complete response; t, translocation; VRd, bortezomib + lenalidomide + dexamethasone.
aCytogenetic risk was assessed by fluorescence in situ hybridization (local testing); high risk was defined as the presence of del17p, t(4;14), or t(14;16) among patients with available cytogenetic risk data, while revised high risk was defined as the presence of del17p, t(4;14), t(14;16), t(14;20), or gain 1q (≥3 copies of chromosome 1q21) among those patients.

Subgroup Analysis of Rates of Sustained MRD-Negativity Lasting ≥12 Months at the 10-5 or 10-6 Sensitivity Thresholds7
Parameter
MRD-Negativity Lasting ≥12 Months, n/N (%)
Sensitivity Threshold of 10-5
Sensitivity Threshold of 10-6
D-VRd
VRd
D-VRd
VRd
ITT (overall)
46/104 (44.2)
13/103 (12.6)
10/104 (9.6)
4/103 (3.9)
OR (95% CI)
5.46 (2.68-11.10)
2.48 (0.76-8.07)
Age
   <65 years
32/76 (42.1)
10/75 (13.3)
7/76 (9.2)
2/75 (2.7)
   OR (95% CI)
4.73 (2.11-10.59)
3.70 (0.74-18.44)
   ≥65 years
14/28 (50.0)
3/28 (10.7)
3/28 (10.7)
2/28 (7.1)
   OR (95% CI)
8.33 (2.04-34.07)
1.56 (0.24-10.14)
ISS disease stage
   I
20/49 (40.8)
3/50 (6.0)
4/49 (8.2)
0/50
   OR (95% CI)
10.80 (2.95-39.60)
NE (NE-NE)
   II
20/40 (50.0)
8/37 (21.6)
6/40 (15.0)
2/37 (5.4)
   OR (95% CI)
3.63 (1.34-9.84)
3.09 (0.58-16.38)
   III
6/14 (42.9)
2/14 (14.3)
0/14
2/14 (14.3)
   OR (95% CI)
4.50 (0.72-28.15)
NE (NE-NE)
Cytogenetic riska
   High
3/16 (18.8)
2/14 (14.3)
0/16
0/14
   OR (95% CI)
1.38 (0.20-9.77)
NE (NE-NE)
   Standard
42/82 (51.2)
11/83 (13.3)
10/82 (12.2)
4/83 (4.8)
   OR (95% CI)
6.87 (3.19-14.82)
2.74 (0.82-9.13)
Revised cytogenetic riska
   High
14/42 (33.3)
6/37 (16.2)
1/42 (2.4)
2/37 (5.4)
   OR (95% CI)
2.58 (0.87-7.64)
0.43 (0.04-4.91)
   Standard
31/56 (55.4)
7/60 (11.7)
9/56 (16.1)
2/60 (3.3)
   OR (95% CI)
9.39 (3.64-24.23)
5.55 (1.14-26.95)
Gain 1qa
13/34 (38.2)
4/28 (14.3)
1/34 (2.9)
2/28 (7.1)
   OR (95% CI)
3.71 (1.05-13.15)
0.39 (0.03-4.59)
≥CR
44/82 (53.7)
12/59 (20.3)
10/82 (12.2)
4/59 (6.8)
   OR (95% CI)
4.54 (2.10-9.78)
1.91 (0.57-6.41)
sCR
39/66 (59.1)
8/46 (17.4)
9/66 (13.6)
4/46 (8.7)
   OR (95% CI)
6.86 (2.77-16.99)
1.66 (0.48-5.75)
Abbreviations: CI, confidence interval; ≥CR, complete response or better; del, deletion; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; sCR, stringent complete response; t, translocation; VRd, bortezomib + lenalidomide + dexamethasone.
aCytogenetic risk was assessed by fluorescence in situ hybridization (local testing); high risk was defined as the presence of del17p, t(4;14), or t(14;16) among patients with available cytogenetic risk data, while revised high risk was defined as the presence of del17p, t(4;14), t(14;16), t(14;20), or gain 1q (≥3 copies of chromosome 1q21) among those patients.
PFS by Sustained MRD-Negativity
  • Median PFS by MRD-negativity (at sensitivity thresholds of 10-5 and 10-6) lasting for ≥6 or ≥12 months was NR in any arm.
    • Among patients who achieved durable MRD-negativity at a sensitivity threshold of 10-5, PFS was consistently better in the D-VRd vs VRd arm.
  • PFS was improved in all arms who achieved sustained MRD-negativity lasting ≥6 or ≥12 months compared with patients who did not achieve sustained MRD-negativity, underlying the importance of achieving this surrogate endpoint.
  • Among all patients with sustained MRD-negativity, 1 patient in the D-VRd arm had subsequent disease progression, and 1 patient in the VRd arm died (cause unknown). Both these patients had high cytogenic risk at baseline.

Subgroup Analysis of the GRIFFIN Study in Black vs White Patients

Nooka et al (2020)19 presented a subgroup analysis from the randomized portion of the GRIFFIN study, evaluating the differences in safety and efficacy of D-VRd vs VRd for Black and White patients at a median follow-up of 22.1 months. Nooka et al (2022) reported 2 updated results in this subgroup analysis at the median follow-up of 27.4 months20 and 38.6 months21.The results presented by Nooka et al (2024)8 regarding the updated post hoc analysis categorized by race during the final analysis in the general population, with approximately ~2 years of additional follow-up at a median follow-up duration of 49.6 months, are outlined as follows:

Study Design/Methods

  • The study design is consistent with the randomized portion of the GRIFFIN Study Design/Methods.
  • This analysis was conducted at the time of final analysis, with an additional ~2-year follow-up.
  • Patients self-reported race and ethnicity.

Results

Patient Characteristics
  • Of the 207 randomized patients included in the study, 15.5% were Black (D-VRd, n=14; VRd, n=18), 77.8% were White (D-VRd, n=85; VRd, n=76), 1% were Asian (VRd, n=2), 1.5% reported “other” race (D-VRd, n=2; VRd, n=1), 0.5% reported multiple races (VRd, n=1), and 3.4% reported unknown race (D-VRd, n=2; VRd, n=5).
    • Additionally, 7.2% were Hispanic or Latino (D-VRd, n=9; VRd, n=6), 89.4% were non-Hispanic or Latino (D-VRd, n=92; VRd, n=93), and 3.4% did not know or did not report ethnicity (D-VRd, n=3; VRd, n=4).
  • The median duration of follow-up was 49.6 months.
  • The baseline patient and disease characteristics are presented in Table: Baseline Patient and Disease Characteristics According to Race.
  • Treatment exposure and duration have been summarized in Table: Summary of Treatment Duration and Exposure According to Race.

Baseline Patient and Disease Characteristics According to Racea,22
Characteristic
Black
White
D-VRd
(n=14)
VRd
(n=18)
D-VRd
(n=85)
VRd
(n=76)
Median age (range), years
58.5 (29-67)
57.0 (48-67)
59.0 (35-70)
61.5 (41-70)
Sex, n (%)
   Male
5 (35.7)
8 (44.4)
52 (61.2)
46 (60.5)
   Female
9 (64.3)
10 (55.6)
33 (38.8)
30 (39.5)
Median weight (range), kg
82.6
(66.0-147.5)
93.8
(57.0-123.8)
78.4
(48.8-158.6)
82.4
(37.4-150.1)
Median height (range), cm
168.3
(152.0-190.5)
168.9
(154.9-190.0)
171.3
(152.4-203.2)
173.0
(150.6-200.0)
BMI
   Median (range), kg/m2
30.7
(23.5-40.6)
31.4
(23.8-43.8)
26.5
(19.7-41.4)
27.3
(15.8-45.0)
   ≥30 kg/m2, n (%)
7 (50.0)
11 (61.1)
29 (34.1)
20 (26.3)
Comorbidities
   Median (range) number of
   comorbiditiesb
7.0 (3-13)
5.5 (1-38)
7.0 (1-24)
7.0 (1-27)
   Diabetes mellitus, n (%)
3 (21.4)
4 (22.2)
9 (10.6)
7 (9.2)
   Pre-existing neuropathies, n (%)c
4 (28.6)
3 (16.7)
4 (4.7)
12 (15.8)
ECOG PS score, n (%)d
n=13
n=18
n=84
n=75
   0
6 (46.2)
7 (38.9)
32 (38.1)
30 (40.0)
   1
6 (46.2)
10 (55.6)
42 (50.0)
37 (49.3)
   2
1 (7.7)
1 (5.6)
10 (11.9)
8 (10.7)
Type of myeloma, n (%)e
n=13
n=18
n=82
n=74
   IgG
8 (61.5)
11 (61.1)
46 (56.1)
40 (54.1)
   IgA
1 (7.7)
2 (11.1)
17 (20.7)
16 (21.6)
   IgD
0
0
1 (1.2)
1 (1.4)
   IgM
0
0
1 (1.2)
0
   Light chain
3 (23.1)
4 (22.2)
17 (20.7)
14 (18.9)
   Biclonal
1 (7.7)
1 (5.6)
0
3 (4.1)
ISS disease stage, n (%)f
   I
9 (64.3)
11 (61.1)
40 (47.1)
37 (48.7)
   II
3 (21.4)
4 (22.2)
32 (37.6)
27 (35.5)
   III
2 (14.3)
3 (16.7)
12 (14.1)
10 (13.2)
   Missing
0
0
1 (1.2)
2 (2.6)
Cytogenetic risk, n (%)g
n=14
n=16
n=80
n=73
   Standard risk
11 (78.6)
14 (87.5)
68 (85.0)
63 (86.3)
   High risk
3 (21.4)
2 (12.5)
12 (15.0)
10 (13.7)
      del(17p)
2 (14.3)
0
6 (7.5)
6 (8.2)
      t(4;14)
1 (7.1)
2 (12.5)
6 (7.5)
3 (4.1)
      t(14;16)
0
0
1 (1.3)
2 (2.7)
Revised cytogenetic risk, n (%)h
n=14
n=16
n=80
n=73
   Standard risk (0 HRCAs)
10 (71.4)
9 (56.3)
44 (55.0)
46 (63.0)
   High risk
4 (28.6)
7 (43.8)
36 (45.0)
27 (37.0)
      gain/amp(1q21)
2 (14.3)
4 (25.0)
30 (37.5)
23 (31.5)
      t(14;20)
0
1 (6.3)
1 (1.3)
0
      1 HRCA
3 (21.4)
6 (37.5)
28 (35.0)
20 (27.4)
      ≥2 HRCAs
1 (7.1)
1 (6.3)
8 (10.0)
7 (9.6)
Abbreviations: BMI, body mass index; D-VRd, DARZALEX + lenalidomide + bortezomib + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; HRCA, high-risk cytogenetic abnormality; Ig, immunoglobulin; ISS, International Staging System; VRd, lenalidomide + bortezomib + dexamethasone.
aDemographic and clinical characteristics were taken from electronic case report forms completed by study sites.
bMedian (range) number of comorbidities was calculated from data of patients with medical histories available in which comorbidities were reported, which included 32 Black patients (D-VRd, n=14; VRd, n=18) and 153 White patients (D-VRd, n=81; VRd, n=72). A value of “0” was not automatically applied in the event a medical history did not report the presence of a comorbidity.
cNeuropathies included peripheral sensory neuropathy, neuralgia, peripheral neuropathy, and/or diabetic neuropathy.
dECOG PS is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
eType of myeloma by immunofixation or serum free light-chain assay.
fISS disease stage is based on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease.
gCytogenetic risk was assessed by FISH (local testing); high risk was defined as the presence of del(17p), t(4;14), or t(14;16) among patients with available cytogenetic risk data.
hRevised cytogenetic risk was assessed by FISH testing; revised high risk was defined as ≥1 of the following: del(17p), t(4;14), t(14;16), t(14;20), or gain/amp(1q21) (≥3 copies of chromosome 1q21).

Summary of Treatment Duration and Exposure According to Racea,22
Parameter
Black
White
D-VRd
(n=14)
VRd
(n=18)
D-VRd
(n=83)
VRd
(n=74)
Median duration of therapy (range), months
32.3
(19.4-36.9)
26.5
(2.6-35.3)
32.5
(1.1-37.7)
31.1
(0.5-36.3)
Median dose intensity (range)
   D (mg/kg/cycle)b
20.3
(19.4-22.7)
-
20.3
(18.9-48.5)
-
   R (mg/cycle)c
245.5
(136.6-311.7)
253.6
(102.2-350.0)
245.0
(71.7-350.0)
274.2
(85.5-350.0)
   V (mg/m2/cycle)d
4.8 (3.1-5.1)
4.8 (3.6-5.3)
5.0 (2.8-5.4)
4.8 (2.5-5.4)
   d (mg/cycle)e
38.4
(33.4-73.3)
114.2
(40.0-120.0)
36.8
(26.6-113.3)
111.7
(44.5-120.0)
Cycle delays, n (%)
9 (64.3)
10 (55.6)
52 (62.7)
34 (45.9)
   D
9 (64.3)
-
50 (60.2)
-
   R
7 (50.0)
9 (50.0)
43 (51.8)
34 (45.9)
   V
1 (7.1)
5 (27.8)
16 (19.3)
14 (18.9)
   d
8 (57.1)
5 (27.8)
38 (45.8)
17 (23.0)
Dose adjusted, n (%)
   D
9 (64.3)
-
39 (47.0)
-
   R
7 (50.0)
11 (61.1)
43 (51.8)
32 (43.2)
   V
4 (28.6)
6 (33.3)
17 (20.5)
14 (18.9)
   d
1 (7.1)
1 (5.6)
9 (10.8)
12 (16.2)
Abbreviations: D, DARZALEX; d, dexamethasone; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; R, lenalidomide; V, bortezomib; VRd, bortezomib + lenalidomide + dexamethasone.
aThe safety analysis population included all randomized patients who received ≥1 dose of study treatment.
bDose intensity (mg/kg/cycle) was calculated as the sum of total doses (mg/kg) received in all cycles divided by the number of treatment cycles on D.
cDose intensity (mg/cycle) was calculated as the sum of total doses (mg) received in all cycles divided by the number of treatment cycles on R.
dDose intensity (mg/m2/cycle) was calculated as the sum of total doses (mg/m2) received in all cycles divided by the number of treatment cycles on V.
eDose intensity (mg/cycle) was calculated as the sum of total doses (mg) received in all cycles divided by the number of treatment cycles on d.
Efficacy
  • Among Black vs White patients, efficacy response rates were evaluable in 32 vs 155, and MRD-negativity was evaluable in 32 vs 161. The efficacy outcomes are summarized in Table: Response, MRD, and Survival Outcomes According to Race.
  • D-VRd reduced the risk of disease progression or death compared with VRd by 55% (HR, 0.45; 95% CI, 0.21-0.95) in the overall population.
    • The risk of disease progression or death was reduced by 61% in Black patients (HR, 0.39; 95% CI, 0.07-2.24; P=0.2767) vs 53% in White patients (HR, 0.47; 95% CI, 0.19-1.18; P=0.1003) in the D-VRd vs VRd arm.

Response, MRD, and Survival Outcomes According to Racea, 8,22
Parameter
Black
White
D-VRd
VRd
D-VRd
VRd
Response evaluable population, n
14
18
83
72
   ≥CR, n (%)
14 (100)
10 (55.6)
67 (80.7)
44 (61.1)
      OR (95% CI)
NE (NE-NE)
2.66 (1.29-5.49)
   sCR, n (%)
13 (92.9)
7 (38.9)
54 (65.1)
36 (50.0)
      OR (95% CI)
20.43 (2.17-192.64)
1.86 (0.98-3.55)
   ≥VGPR, n (%)
14 (100)
16 (88.9)
79 (95.2)
53 (73.6)
      OR (95% CI)
NE (NE-NE)
7.08 (2.28-21.98)
   PR, %
-
5.6
3.6
18.1
   SD/PD/NE, %
-
5.6
1.2
8.3
MRD-evaluable populationb, n
14
18
85
76
   MRD at 10-5 threshold, n (%)
9 (64.3)
4 (22.2)
56 (65.9)
24 (31.6)
      OR (95% CI)
6.30 (1.33-29.94)
4.18 (2.16-8.09)
   MRD at 10-6 threshold, n (%)
4 (28.6)
2 (11.1)
33 (38.8)
11 (14.5)
      OR (95% CI)
3.20 (0.49-20.81)
3.75 (1.73-8.13)
Estimated 48-month PFS rate, %
79.1
64.6
89.4
74.2
Abbreviations: CI, confidence interval; CR, complete response; ≥CR, complete response or better; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; MRD, minimal residual disease; NE, not evaluable; NGS, next-generation sequencing; OR, odds ratio; PD, progressive disease; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.
aPercentages may not add to 100 due to rounding.
bThe threshold of MRD negativity was defined as 1 tumor cell per 105 or per 106 white cells. MRD status is based on the assessment of bone marrow aspirates by NGS in accordance with International Myeloma Working Group criteria. Bone marrow aspirates were assessed at baseline, at first evidence of suspected CR or sCR (including patients with ≥VGPR and suspected daratumumab interference), at the end of induction and consolidation, and after 1 and 2 years (±3 weeks) of maintenance, regardless of response.
Safety
  • TEAEs are summarized in Table: Most common (≥30%) TEAEs in Black or White patients.
  • The most common serious TEAE was pneumonia in both Black (D-VRd, 21.4%; VRd, 16.7%) and White patients (D-VRd, 13.3%; VRd, 14.9%).
  • Study treatment was discontinued among Black (D-VRd, 28.6% [n=4]; VRd, 61.1% [n=11]) and White patients (D-VRd, 22.4% [n=19]; VRd, 47.4% [n=36]).
    • Primary reasons for treatment discontinuation were progressive disease (Black: D-VRd, 0% [n=0]; VRd, 22.2% [n=4]; White: 8.2% [n=7]; 11.8% [n=9]) and adverse events (Black: D-VRd, 14.3% [n=2]; VRd, 11.1% [n=2]; White: D-VRd, 5.9% [n=5]; VRd, 13.2% [n=10]).
  • TEAEs that led to study treatment discontinuation of ≥1 component of study combination therapy occurred in 64.3% vs 38.9% of Black and 28.9% vs 25.7% of White patients in the D-VRd vs VRd arm. Summary of TEAEs leading to study treatment discontinuation according to race is presented in Table: Summary of TEAEs Leading to Discontinuation of Study Treatment According to Race Occurring in ≥2 Patients in Any Treatment Group or Those Attributed to Neuropathy-Related Events.
  • No deaths were reported in Black patients during the whole duration of the study (treatment period and post-treatment observation combined); 12 deaths were reported in White patients (D-VRd, n=6; VRd, n=6) due to PD (D-VRd, n=4; VRd, n=4) and AEs (D-VRd, n=2 [1 event occurred outside the reporting interval, which was >30 days after the last dose of study treatment]; VRd, n=2 [both events occurred outside the reporting interval]).
  • No deaths due to TEAEs were reported among Black patients in either arm, and 1 death due to pneumonia was reported among White patients in the D-VRd arm.

Most common (≥30%) TEAEs in Black or White patientsa,8
Adverse Event, n (%)
Black
White
D-VRd
(n=14)
VRd
(n=18)
D-VRd
(n=83)
VRd
(n=74)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Hematologic
   Neutropenia
8 (57.1)
7 (50.0)
6 (33.3)
4 (22.2)
54 (65.1)
39 (47.0)
26 (35.1)
13 (17.6)
   Anemia
8 (57.1)
2 (14.3)
7 (38.9)
3 (16.7)
29 (34.9)
7 (8.4)
22 (29.7)
3 (4.1)
   Thrombocytopenia
6 (42.9)
4 (28.6)
7 (38.9)
2 (11.1)
38 (45.8)
12 (14.5)
26 (35.1)
6 (8.1)
   Leukopenia
6 (42.9)
3 (21.4)
8 (44.4)
1 (5.6)
32 (38.6)
14 (16.9)
17 (23.0)
4 (5.4)
   Lymphopenia
5 (35.7)
4 (28.6)
9 (50.0)
7 (38.9)
26 (31.3)
19 (22.9)
16 (21.6)
12 (16.2)
Nonhematologic
   Upper respiratory tract
   infection
11 (78.6)
0
9 (50.0)
0
55 (66.3)
4 (4.8)
38 (51.4)
2 (2.7)
   Constipation
9 (64.3)
0
7 (38.9)
0
40 (48.2)
2 (2.4)
28 (37.8)
1 (1.4)
   Peripheral oedema
9 (64.3)
0
9 (50.0)
0
27 (32.5)
2 (2.4)
27 (36.5)
3 (4.1)
   Peripheral
   neuropathy/peripheral
   sensory neuropathy
8 (57.1)
1 (7.1)
12 (66.7)
1 (5.6)
53 (63.9)
5 (6.0)
58 (78.4)
6 (8.1)
   Nausea
8 (57.1)
1 (7.1)
9 (50.0)
1 (5.6)
42 (50.6)
1 (1.2)
37 (50.0)
0
   Fatigue
8 (57.1)
1 (7.1)
8 (44.4)
0
61 (73.5)
6 (7.2)
45 (60.8)
5 (6.8)
   Headache
7 (50.0)
0
2 (11.1)
0
26 (31.3)
5 (6.0)
17 (23.0)
1 (1.4)
   Vomiting
7 (50.0)
1 (7.1)
5 (27.8)
0
25 (30.1)
2 (2.4)
21 (28.4)
0
   Arthralgia
7 (50.0)
1 (7.1)
5 (27.8)
0
31 (37.3)
0
28 (37.8)
2 (2.7)
   Cough
7 (50.0)
0
5 (27.8)
0
45 (54.2)
0
21 (28.4)
0
   Insomnia
7 (50.0)
0
2 (11.1)
0
37 (44.6)
2 (2.4)
26 (35.1)
1 (1.4)
   Rash maculopapular
6 (42.9)
1 (7.1)
2 (11.1)
0
18 (21.7)
2 (2.4)
19 (25.7)
2 (2.7)
   Pyrexia
6 (42.9)
0
3 (16.7)
0
41 (49.4)
3 (3.6)
26 (35.1)
2 (2.7)
   Diarrhea
6 (42.9)
0
6 (33.3)
0
59 (71.1)
7 (8.4)
46 (62.2)
4 (5.4)
   Decreased appetite
6 (42.9)
0
2 (11.1)
0
18 (21.7)
0
8 (10.8)
0
   Back pain
5 (35.7)
0
9 (50.0)
0
35 (42.2)
2 (2.4)
22 (29.7)
3 (4.1)
   Pain in extremity
5 (35.7)
0
7 (38.9)
0
17 (20.5)
1 (1.2)
15 (20.3)
0
   Myalgia
5 (35.7)
0
4 (22.2)
0
21 (25.3)
0
15 (20.3)
2 (2.7)
   Hypokalemia
5 (35.7)
0
6 (33.3)
1 (5.6)
23 (27.7)
4 (4.8)
16 (21.6)
2 (2.7)
   Dizziness
4 (28.6)
0
7 (38.9)
0
19 (22.9)
0
15 (20.3)
0
   Dysgeusia
4 (28.6)
0
6 (33.3)
0
19 (22.9)
0
12 (16.2)
0
   Dyspnea
3 (21.4)
0
6 (33.3)
2 (11.1)
21 (25.3)
2 (2.4)
21 (28.4)
2 (2.7)
   Hyperglycemia
1 (7.1)
0
6 (33.3)
0
11 (13.3)
2 (2.4)
11 (14.9)
1 (1.4)
   Muscle spasms
3 (21.4)
0
2 (11.1)
0
26 (31.3)
2 (2.4)
15 (20.3)
1 (1.4)
Abbreviations: D-VRd, daratumumab + lenalidomide + bortezomib + dexamethasone; IRR, infusion-related reaction; TEAE, treatment-emergent adverse event; VRd, lenalidomide + bortezomib + dexamethasone.aThe safety analysis population included all randomized patients who received ≥1 dose of study treatment.bIRRs (not shown in table) occurred in 28.6% of Black patients and 53.0% of White patients who received D-VRd; 1 (7.1%) Black patient and 6 (7.2%) White patients had grade 3 IRRs (none were grade 4 or 5).

Summary of TEAEs Leading to Discontinuation of Study Treatment According to Race Occurring in ≥2 Patients in Any Treatment Group or Those Attributed to Neuropathy-Related Eventsa,b,22
Black
D-VRd
(n=14)
VRd
(n=18)
Discontinuation of
Discontinuation of
Any Study Treatment
D
R
V
d
Any Study Treatment
R
V
d
6Patients with TEAEs leading to study treatment discontinuation, n (%)
9 (64.3)
1 (7.1)
2 (14.3)
8 (57.1)
1 (7.1)
7 (38.9)
2 (11.1)
5 (27.8)
1 (5.6)
   Occurring in ≥2 patients or attributable to neuropathy-related events
      Peripheral sensory
      neuropathy
3 (21.4)
0
0
3 (21.4)
0
4 (22.2)
0
4 (22.2)
0
      Neuralgia
2 (14.3)
0
0
2 (14.3)
0
1 (5.6)
1 (5.6)
0
0
      Hypoesthesia
1 (7.1)
0
0
1 (7.1)
0
0
0
0
0
      Peripheral
      neuropathy
1 (7.1)
0
1 (7.1)
1 (7.1)
0
0
0
0
0
      Paresthesia
0
0
0
0
0
1 (5.6)
0
1 (5.6)
0
White
D-VRd
(n=83)
VRd
(n=74)
Discontinuation of
Discontinuation of
Any Study Treatment
D
R
V
d
Any Study Treatment
R
V
d
Patients with TEAEs leading to study treatment discontinuation, n (%)
24 (28.9)
5 (6.0)
12 (14.5)
15 (18.1)
7 (8.4)
19 (25.7)
11 (14.9)
12 (16.2)
9 (12.2)
   Occurring in ≥2 patients or attributable to neuropathy-related events
      Peripheral sensory
      neuropathy
8 (9.6)
0
0
8 (9.6)
0
3 (4.1)
1 (1.4)
3 (4.1)
1 (1.4)
      Neuralgia
2 (2.4)
0
0
2 (2.4)
0
2 (2.7)
0
2 (2.7)
0
      Neutropenia
2 (2.4)
0
2 (2.4)
0
0
0
0
0
0
      Rash
2 (2.4)
0
2 (2.4)
0
0
0
0
0
0
      Peripheral
      neuropathy
1 (1.2)
0
0
1 (1.2)
0
4 (5.4)
2 (2.7)
3 (4.1)
2 (2.7)
      Fall
0
0
0
0
0
1 (1.4)
0
1 (1.4)
0
Abbreviations: D, daratumumab; d, dexamethasone; D-VRd, daratumumab + lenalidomide + bortezomib + dexamethasone; R, lenalidomide; TEAE, treatment-emergent adverse event; V, bortezomib; VRd, lenalidomide + bortezomib + dexamethasone.
aThe safety analysis population included all randomized patients who received ≥1 dose of study treatment.
bNeuropathy-related events included peripheral sensory neuropathy, neuralgia, paresthesia, peripheral neuropathy, hypoesthesia, and/or falls.

Final Analysis in Clinically Relevant Subgroups

Chari et al (2024)9,23 reported the final efficacy and safety analysis results of clinically relevant subgroups from the GRIFFIN study (median follow-up, 49.6 months).

Study Design/Methods

  • This final analysis was conducted after all patients completed ≥1 year of follow-up after concluding study treatment, died, or withdrew.

Results

Efficacy
  • MRD-negativity (10-5) rates favored the D-VRd vs VRd arm across all subgroups at the time of final analysis. See Table: Final Analysis of MRD-negativity (10-5) Rates by the End of the GRIFFIN Study.
  • A final analysis of sCR rates were higher for D-VRd vs VRd for most subgroups. See Table: Final Analysis of sCR by the End of the GRIFFIN Study.
  • MRD-negativity (10-5) rates favored the D-VRd vs VRd arm across all subgroups among patients who achieved a best response ≥CR by the end of the study. See Table: Final Analysis of MRD-negativity (10-5) Rates Among Patients with a Best Response of ≥CR by the End of the GRIFFIN Study.
  • D-VRd was associated with higher rates of sustained MRD-negativity (10-5) lasting ≥12 months across all subgroups. See Table: Final Analysis of Rates of Sustained MRD-negativity (10-5) lasting ≥12 months.
    • No patients who achieved sustained MRD-negativity (10-5) lasting ≥12 months developed PD.
  • Among MRD-evaluable patients who achieved MRD-negativity (10-5) at any time, 2 (both with ≥2 HRCAs) patients in the D-VRd arm and 5 (0 HRCA, n=2; 1 HRCA, n=3) patients in the VRd arm developed PD.
    • Two patients from the D-VRd arm and 3 patients from the VRd arm, who initially achieved MRD-negativity, developed PD after they became MRD positive again. The remaining 2 patients from the VRd arm developed PD while they continued to be MRD negative; however, MRD was not evaluated around the time of PD.
  • At a median follow-up of 49.6 months, the HR point estimates for PFS among all subgroups with cytogenetic abnormalities favored the D-VRd vs VRd arm, except for patients with ≥2 HRCAs. See Table: Final Analysis of PFS in the GRIFFIN Study.
    • Median PFS was not reached for either treatment group among patients with 0 HRCA, and the PFS HR was 0.39 (95% CI, 0.10-1.51) for D-VRd vs VRd.
    • Median PFS was not reached for D-VRd and was 47.9 months for VRd among patients with 1 HRCA, and the PFS HR was 0.19 (95% CI, 0.05-0.75) for D-VRd vs VRd.
    • Median PFS was 33.9 months for D-VRd and was not reached for VRd among patients with ≥2 HRCAs, (HR, 1.65; 95% CI, 0.30-9.18).
    • PFS was not reached for D-VRd and was 47.9 months for VRd among patients with gain/amp(1q21), with or without HRCAs, and the PFS HR was 0.42 (95% CI, 0.14-1.27) for D-VRd vs VRd.
  • Within the functionally high-risk subgroup of patients with a best response of <VGPR by the end of induction, more D-VRd vs VRd patients had revised high cytogenetic risk and 1 HRCA at baseline, and similar proportions had ≥2 HRCAs.
    • Revised high risk: 48.3% (n=14/29) vs 32.6% (n=14/43), D-VRd vs VRd respectively.
    • 1 HRCA: 37.9% (n=11/29) vs 23.3% (n=10/43), D-VRd vs VRd respectively.
    • ≥2 HRCAs: 10.3% (n=3/29) vs 9.3% (n=4/43), D-VRD vs VRd respectively.
  • Among patients who did not achieve MRD-negativity (10-5)by the end of consolidation, the proportion of patients with revised high cytogenetic risk, 1 HRCA, and ≥2 HRCAs was higher for D-VRd vs VRd at baseline.
    • Revised high risk: 52.1% (n=25/48) vs 34.2% (n=26/76), D-VRd vs VRd respectively.
    • 1 HRCA: 39.6% (n=19/48) vs 25.0% (n=19/76), D-VRd vs VRd respectively.
    • ≥2 HRCAs: 12.5% (n=6/48) vs 9.2% (n=7/76), D-VRd vs VRd respectively.

Final Analysis of MRD-negativity (10-5) Rates by the End of the GRIFFIN Study9
Subgroup
D-VRd, n/N (%)
VRd, n/N (%)
OR (95% CI)a
ITT (overall)
67/104 (64.4)
31/103 (30.1)
4.23 (2.35-7.62)
Baseline characteristic
   Age ≥65 years
19/28 (67.9)
5/28 (17.9)
9.71 (2.78-33.92)
   ISS stage III disease
10/14 (71.4)
5/14 (35.7)
4.50 (0.91-22.15)
   Cytogenetic risk
      High cytogenetic riskb
7/16 (43.8)
4/14 (28.6)
1.94 (0.42-8.92)
      Revised high cytogenetic riskc
23/42 (54.8)
12/37 (32.4)
2.52 (1.01-6.32)
      0 HRCAc
42/56 (75.0)
19/60 (31.7)
6.47 (2.87-14.60)
      1 HRCAc
17/32 (53.1)
11/29 (37.9)
1.85 (0.67-5.15)
      ≥2 HRCAsc
6/10 (60.0)
1/8 (12.5)
10.50 (0.91-121.39)
      Gain/amp(1q21)d
21/34 (61.8)
8/28 (28.6)
4.04 (1.38-11.81)
      Gain/amp(1q21) + 1 HRCAc
6/9 (66.7)
0/6
NE (NE-NE)
      Gain/amp(1q21) isolatede
15/25 (60.0)
8/22 (36.4)
2.62 (0.81-8.55)
Best response to therapy
   <VGPR after induction
17/30 (56.7)
8/44 (18.2)
5.88 (2.05-16.86)
   ≥VGPR after induction
50/70 (71.4)
22/54 (40.7)
3.64 (1.72-7.70)
Abbreviations: CI, confidence interval; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; FISH, fluorescence in situ hybridization; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.
aMantel-Haenszel estimate of the common OR for unstratified tables is used. An OR >1 indicates an advantage for D-VRd.
bHigh-risk cytogenetics are defined based on FISH testing as ≥1 of the following: del17p, t(4;14), or t(14;16).
cRevised high-risk cytogenetics are defined based on FISH testing as ≥1 HRCA: del17p, t(4;14), t(14;16), t(14;20), or gain/amp(1q21) (≥3 copies of chromosome 1q21).
dPatients in this group had gain/amp(1q21) with or without other HRCAs (del17p, t[4;14], t[14;16], or t[14;20]).
ePatients with isolated gain/amp(1q21) did not have any other HRCAs.

Final Analysis of sCR by the End of the GRIFFIN Study23
Subgroup
D-VRd, n/N (%)
VRd, n/N (%)
OR (95% CI)a
Response evaluable (overall)b
67/100 (67.0%)
47/98 (48.0%)
2.18 (1.22-3.89)
Baseline characteristic
   Age ≥65 years
17/27 (63.0)
11/27 (40.7)
2.47 (0.83-7.39)
   ISS stage III disease
9/14 (64.3)
8/13 (61.5)
1.13 (0.24-5.37)
   Cytogenetic risk
      High cytogenetic riskc
8/16 (50.0)
5/13 (38.5)
1.60 (0.36-7.07)
      Revised high cytogenetic riskd
23/41 (56.1)
20/36 (55.6)
1.02 (0.42-2.52)
      0 HRCAd
43/55 (78.2)
26/58 (44.8)
4.41 (1.94-10.04)
      1 HRCAd
18/31 (58.1)
17/28 (60.7)
0.90 (0.32-2.54)
      ≥2 HRCAsd
5/10 (50.0)
3/8 (37.5)
1.67 (0.25-11.07)
      Gain/amp(1q21)e
19/33 (57.6)
16/28 (57.1)
1.02 (0.37-2.82)
      Gain/amp(1q21) + 1 HRCAd
5/9 (55.6)
2/6 (33.3)
2.50 (0.29-21.40)
      Gain/amp(1q21) isolatedf
14/24 (58.3)
14/22 (63.6)
0.80 (0.24-2.63)
Best response to therapy
   <VGPR by the end of induction
20/30 (66.7)
10/44 (22.7)
6.80 (2.41-19.16)
   ≥VGPR by the end of induction
47/70 (67.1)
37/54 (68.5)
0.94 (0.44-2.01)
MRD status
   Not MRD- by the end of consolidation
24/48 (50.0)
32/78 (41.0)
1.44 (0.70-2.96)
   MRD- by the end of consolidation
43/52 (82.7)
15/20 (75.0)
1.59 (0.46-5.51)
Abbreviations: CI, confidence interval; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; FISH, fluorescence in situ hybridization; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; MM, multiple myeloma; MRD, minimal residual disease; OR, odds ratio; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.
aMantel-Haenszel estimate of the common OR for unstratified tables is used. An OR >1 indicates an advantage for D-VRd.
bThis analysis included patients from the response evaluable population, which included all randomized patients who had measurable disease (confirmed MM diagnosis), received ≥1 dose of study treatment, and had ≥ postbaseline disease assessment.
cHigh-risk cytogenetics are defined based on FISH testing as ≥1 of the following: del17p, t(4;14), or t(14;16).
dRevised high-risk cytogenetics are defined based on FISH testing as ≥1 HRCA: del17p, t(4;14), t(14;16), t(14;20), or gain/amp(1q21) (≥3 copies of chromosome 1q21).
ePatients in this group had gain/amp(1q21) with or without other HRCAs (del17p, t[4;14], t[14;16], or t[14;20]).
fPatients with isolated gain/amp(1q21) did not have any other HRCAs.

Final Analysis of MRD-negativity (10-5) Rates Among Patients with a Best Response of ≥CR by the End of the GRIFFIN Study9
Subgroup
D-VRd, n/N (%)
VRd, n/N (%)
OR (95% CI)a
Patients with best response of ≥CRb
64/83 (77.1)
28/59 (47.5)
3.70 (1.77-7.72)
Baseline characteristic
   Age ≥65 years
18/23 (78.3)
5/14 (35.7)
6.48 (1.48-28.34)
   ISS stage III disease
10/13 (76.9)
4/8 (50.0)
3.33 (0.50-22.14)
   Cytogenetic risk
      High cytogenetic riskc
6/10 (60.0)
4/7 (57.1)
1.13 (0.16-7.99)
      Revised high cytogenetic riskd
21/30 (70.0)
12/23 (52.2)
2.14 (0.69-6.63)
      0 HRCAd
41/49 (83.7)
16/35 (45.7)
6.09 (2.22-16.68)
      1 HRCAd
16/24 (66.7)
11/20 (55.0)
1.64 (0.48-5.56)
      ≥2 HRCAsd
5/6 (83.3)
1/3 (33.3)
10.0 (0.40-250.42)
      Gain/amp(1q21)e
19/25 (76.0)
8/17 (47.1)
3.56 (0.95-13.37)
      Gain/amp(1q21) + 1 HRCAd
5/6 (83.3)
0/2
NE (NE-NE)
      Gain/amp(1q21) isolatedf
14/19 (73.7)
8/15 (53.3)
2.45 (0.58-10.33)
Best response to therapy
   <VGPR by the end of induction
16/22 (72.7)
7/15 (46.7)
3.05 (0.77-12.14)
   ≥VGPR by the end of induction
48/61 (78.7)
21/44 (47.7)
4.04 (1.73-9.48)
Abbreviations: CI, confidence interval; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; FISH, fluorescence in situ hybridization; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; MM, multiple myeloma; MRD, minimal residual disease; OR, odds ratio; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.
aMantel-Haenszel estimate of the common OR for unstratified tables is used. An OR >1 indicates an advantage for D-VRd.
bThis analysis included patients from the response evaluable population, which included all randomized patients who had measurable disease (confirmed MM diagnosis), received ≥1 dose of study treatment, and had ≥ postbaseline disease assessmentcHigh-risk cytogenetics are defined based on FISH testing as ≥1 of the following: del17p, t(4;14), or t(14;16).
dRevised high-risk cytogenetics are defined based on FISH testing as ≥1 HRCA: del17p, t(4;14), t(14;16), t(14;20), or gain/amp(1q21) (≥3 copies of chromosome 1q21).
ePatients in this group had gain/amp(1q21) with or without other HRCAs (del17p, t[4;14], t[14;16], or t[14;20]).
fPatients with isolated gain/amp(1q21) did not have any other HRCAs.

Final Analysis of Rates of Sustained MRD-negativity (10-5) lasting ≥12 months9
Subgroup
D-VRd, n/N (%)
VRd, n/N (%)
OR (95% CI)a
ITT (overall)
46/104 (44.2)
14/103(13.6)
5.0 (2.50-9.99)
Baseline characteristic
   Age ≥65 years
14/28 (50.0)
3/28 (10.7)
8.33 (2.04 (34.07)
   ISS stage III disease
6/14 (42.9)
2/14 (14.3)
4.50 (0.72-28.15)
   Cytogenetic risk
      High cytogenetic riskb
3/16 (18.8)
2/14 (14.3)
1.38 (0.20-9.77)
      Revised high cytogenetic riskc
14/42 (33.3)
6/37 (16.2)
2.58 (0.87-7.64)
      0 HRCAc
31/56 (55.4)
8/60 (13.3)
8.06 ((3.24-20.06)
      1 HRCAc
12/32 (37.5)
5/29 (17.2)
2.88 (0.87-9.56)
      ≥2 HRCAsc
2/10 (20.0)
1/8 (12.5)
1.75 (0.13-23.70)
      Gain/amp(1q21)d
13/34 (38.2)
4/28 (14.3)
3.71 (1.05-13.15)
      Gain/amp(1q21) + 1 HRCAc
2/9 (22.2)
0/6
NE (NE-NE)
      Gain/amp(1q21) isolatede
11/25 (44.0)
4/22 (18.2)
3.54 (0.93-13.51)
Best response to therapy
   <VGPR by the end of induction
13/30 (43.3)
3/44 (6.8)
10.45 (2.64-41.41)
   ≥VGPR by the end of induction
33/70 (47.1)
11/54 (20.4)
3.49 (1.55-7.85)
Abbreviations: CI, confidence interval; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; FISH, fluorescence in situ hybridization; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.
aMantel-Haenszel estimate of the common OR for unstratified tables is used. An OR >1 indicates an advantage for D-VRd.
bHigh-risk cytogenetics are defined based on FISH testing as ≥1 of the following: del17p, t(4;14), or t(14;16).
cRevised high-risk cytogenetics are defined based on FISH testing as ≥1 HRCA: del17p, t(4;14), t(14;16), t(14;20), or gain/amp(1q21) (≥3 copies of chromosome 1q21).
dPatients in this group had gain/amp(1q21) with or without other HRCAs (del17p, t[4;14], t[14;16], or t[14;20]).
ePatients with isolated gain/amp(1q21) did not have any other HRCAs.

Final Analysis of PFS in the GRIFFIN Study9
Subgroup
D-VRd
VRd
HR (95% CI)a
n/N
Median PFS, Months
n/N
Median PFS, Months
ITT (overall)
11/104
NR
18/103
NR
0.45 (0.21-0.95)
Baseline characteristic
   Age ≥65 years
2/28
NR
5/28
NR
0.29 (0.06-1.48)
   ISS stage III disease
2/14
NR
6/14
33.1
0.23 (0.05-1.13)
   Cytogenetic risk
      High cytogenetic riskb
5/16
NR
5/14
36.1
0.54 (0.15-1.88)
      Revised high cytogenetic riskc
7/42
NR
10/37
47.9
0.38 (0.14-1.01)
      0 HRCAc
3/56
NR
7/60
NR
0.39 (0.10-1.51)
      1 HRCAc
3/32
NR
8/29
47.9
0.19 (0.05-0.75)
      ≥2 HRCAsc
4/10
33.9
2/8
NR
1.65 (0.30-9.18)
      Gain/amp(1q21)d
6/34
NR
7/28
47.9
0.42 (0.14-1.27)
      Gain/amp(1q21) + 1 HRCAc
4/9
33.9
2/6
38.7
0.81 (0.15-4.47)
      Gain/amp(1q21) isolatede
2/25
NR
5/22
47.9
0.21 (0.04-1.09)
Best response to therapy
   <VGPR by the end of induction
3/30
NR
9/44
NR
0.29 (0.08-1.07)
   ≥VGPR by the end of induction
8/70
NR
9/54
NR
0.58 (0.22-1.51)
MRD status
   Not MRD- by the end of consolidation
9/52
NR
14/82
NR
0.82 (0.35-1.89)
   MRD- by the end of consolidation
2/52
NR
4/21
NR
0.17 (0.03-0.92)
   Not MRD- by the end of 2 yrs of maintenance
8/37
NR
12/72
NR
1.04 (0.43-2.56)
   MRD- by the end of 2 yrs of maintenance
3/67
NR
6/31
NR
0.21 (0.05-0.86)
Abbreviations: CI, confidence interval; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; FISH, fluorescence in situ hybridization; HR, hazard ratio; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; NR, not reached; PFS, progression-free survival; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.
aHR and 95% CI are from a Cox proportional hazards model with treatment as the sole explanatory variable. An HR <1 indicates an advantage for D-VRd.
bHigh-risk cytogenetics are defined based on FISH testing as ≥1 of the following: del17p, t(4;14), or t(14;16).
cRevised high-risk cytogenetics are defined based on FISH testing as ≥1 HRCA: del17p, t(4;14), t(14;16), t(14;20), or gain/amp(1q21) (≥3 copies of chromosome 1q21).
dPatients in this group had gain/amp(1q21) with or without other HRCAs (del17p, t[4;14], t[14;16], or t[14;20]).
ePatients with isolated gain/amp(1q21) did not have any other HRCAs.
Safety
  • A summary of the most common (>30%) TEAEs in the safety analysis population separated by age <65 years and ≥65 years is provided in Table: Most Common (>30%) any grade TEAEs by Age (<65 Years and ≥65 Year).
  • Among patients aged <65 years (84.7% vs 80.0%) and ≥65 years (88.9% vs 77.8%), the rates of grade 3/4 TEAEs were slightly higher for D-VRd vs VRd.
  • The incidence of serious TEAEs was lower in D-VRd vs VRd among patients <65 years, 41.7% vs 56.0% respectively.
  • The incidence of serious TEAEs was higher in the D-VRd vs VRd among patients ≥65 years, 59.3% vs 40.7% respectively.
  • The discontinuation of ≥1 therapeutic agent due to TEAEs were comparable between patients aged <65 years (D-VRd, 31.9% vs VRd, 33.3%) and higher for D-VRd vs VRd in patients ≥65 years (D-VRd, 37.0% vs 25.9%).
    • The most common TEAE leading to discontinuation of ≥1 drug was peripheral neuropathy for patients <65 years (D-VRd, 11.1% vs VRd, 13.3%) and ≥65 years (D-VRd, 18.5% vs VRd, 11.1%).
  • The incidence of TEAEs leading to lenalidomide dose reduction was higher for D-VRd vs VRd (<65 years: D-VRd, 33.3% vs VRd, 28.0%; ≥65 years: D-VRd, 59.3% vs VRd, 33.3%) among patients aged <65 and ≥65 years.
    • The most common TEAE leading to lenalidomide dose reduction was neutropenia for patients <65 years (D-VRd, 15.3% vs VRd, 5.3%) and ≥65 years (D-VRD, 22.2% vs VRd, 14.8%).
  • Two deaths due to a TEAE occurred and were considered unrelated to study treatment.
    • <65 years (VRd, n=1; cause unknown)
    • ≥65 years (D-VRd, n=1; pneumonia)

Most Common (>30%)a any grade TEAEs by Age (<65 Years and ≥65 Year)9
Most common TEAEs, n (%)
<65 Years
≥65 Years
D-VRd
(n=72)
VRd
(n=75)
D-VRd
(n=27)
VRd
(n=27)
Hematologic
   Neutropenia
47 (65.3)
29 (38.7)
16 (59.3)
12 (44.4)
   Thrombocytopenia
 30 (41.7)
24 (32.0)
14 (51.9)
12 (44.4)
   Leukopenia
29 (40.3)
21 (28.0)
10 (37.0)
9 (33.3)
   Anemia
25 (34.7)
25 (33.3)
12 (44.4)
8 (29.6)
   Lymphopenia
23 (31.9)
23 (30.7)
8 (29.6)
6 (22.2)
Nonhematologic
   Upper respiratory tract
   infection
51 (70.8)
37 (49.3)
16 (59.3)
14 (51.9)
   Diarrhea
48 (66.7)
39 (52.0)
18 (66.7)
17 (63.0)
   Fatigue
48 (66.7)
45 (60.0)
23 (85.2)
18 (66.7)
   Peripheral neuropathyb
41 (56.9)
56 (74.7)
21 (77.8)
22 (81.5)
   Nausea
38 (52.8)
37 (49.3)
14 (51.9)
14 (51.9)
   Constipation
37 (51.4)
29 (38.7)
14 (51.9)
13 (48.1)
   Insomnia
36 (50.0)
25 (33.3)
9 (33.3)
6 (22.2)
   Cough
35 (48.6)
26 (34.7)
18 (66.7
5 (18.5)
   Pyrexia
34 (47.2)
27 (36.0)
14 (51.9)
6 (22.2)
   Back pain
30 (41.7)
29 (38.7)
11 (40.7)
7 (25.9)
   Arthralgia
27 (37.5)
26 (34.7)
12 (44.4)
12 (44.4)
   Headache
27 (37.5)
18 (24.0)
6 (22.2)
6 (22.2)
   Muscle spasms
26 (36.1)
11 (14.7)
4 (14.8)
9 (33.3)
   Vomiting
25 (34.7)
21 (28.0)
7 (25.9)
8 (29.6)
   Peripheral edema
24 (33.3)
25 (33.3)
12 (44.4)
12 (44.4)
   Hypokalemia
19 (26.4)
20 (26.7)
9 (33.3)
7 (25.9)
   Pain in extremity
19 (26.4)
13 (17.3)
3 (11.1)
9 (33.3)
   Dyspnea
14 (19.4)
24 (32.0)
10 (37.0)
7 (25.9)
   Dizziness
15 (20.8)
16 (21.3)
8 (29.6)
9 (33.3)
   Pneumonia
14 (19.4)
16 (21.3)
10 (37.0)
2 (7.4)
   Dysgeusia
14 (19.4)
14 (18.7)
9 (33.3)
5 (18.5)
Abbreviations: D-VRd, daratumumab + lenalidomide + bortezomib + dexamethasone; TEAE, treatment-emergent adverse event; VRd, lenalidomide + bortezomib + dexamethasone.
aIncludes TEAEs occurring in ≥30% of patients aged <65 years or ≥65 years in either treatment group from the safety analysis population (all randomized patients who received ≥1 dose of study treatment).
bIncludes preferred terms neuropathy peripheral and peripheral sensory neuropathy.

Analysis of Transplant-Eligible Patients With HRCAs From MASTER and GRIFFIN Studies

Callander et al (2024)10 reported post hoc analysis results evaluating the clinical efficacy of DARZALEX-based quadruplet therapies D-KRd and D-VRd in transplant-eligible patients with NDMM with HRCAs from the MASTER (median follow-up of 31.1 months) and GRIFFIN (median follow-up of 49.6 months) studies, respectively. Results specific to GRIFFIN are summarized below.

Study Design/Methods

  • Patients with HRCA included ≥1 genetic abnormality: del17p, t(4;14), t(14;16), t(14;20), and/or gain/amp(1q21) (≥3 copies of chromosome 1q21).

Results

Patient Characteristics

Baseline Patient and Disease Characteristics in Patients who Received D-VRd in GRIFFINa,10
Characteristic
Standard-Risk
0 HRCA (n=67)
High-Risk
1 HRCA (n=34)
Ultra-High-Risk
≥2 HRCAs (n=13)
Total
(n=114)
Median age (range), years
59.0 (34-70)
59.5 (29-70)
62.0 (49-70)
60.0 (29-70)
Sex, n (%)
   Male
37 (55.2)
18 (52.9)
9 (69.2)
64 (56.1)
   Female
30 (44.8)
16 (47.1)
4 (30.8)
50 (43.9)
ISS disease stage,b n (%)
   I
42 (62.7)
13 (38.2)
5 (38.5)
60 (52.6)
   II
20 (29.9)
17 (50.0)
4 (30.8)
41 (36.0)
   III
5 (7.5)
4 (11.8)
4 (30.8)
13 (11.4)
Cytogenetic abnormality,c n (%)
   del(17p)
0
4 (11.8)
8 (61.5)
12 (10.5)
   t(4;14)
0
3 (8.8)
5 (38.5)
8 (7.0)
   t(14;16)
0
0
1 (7.7)
1 (0.9)
   Gain/amp(1q21)
0
26 (76.5)
12 (92.3)
38 (33.3)
   t(14;20)
0
1 (2.9)
0
1 (0.9)
Median duration of study treatment,d months
   Induction/consolidatione
8.1
8.1
7.4
8.1
   Maintenance
24.4
24.2
23.9
24.2
Abbreviations: ASCT, autologous stem cell transplantation; del, deletion; FISH, fluorescence in situ hybridization; HRCA, high-risk cytogenetic abnormality; ISS, international staging system; t, translocation.
aFor GRIFFIN, the D-VRd group included patients from the randomized phase (n=104) and the safety run-in phase (n=16). Patients were grouped by HRCA: 0 HRCA (n=67), 1 HRCA (n=34), or ≥2 HRCAs (n=13). 6 patients were not evaluable for cytogenetic abnormalities.
bISS disease stage is based on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease.
cCytogenetic risk was assessed by fluorescence in situ hybridization (local testing).
dStudy duration is reported for treated patients for induction/consolidation (0 HRCA, n=66; 1 HRCA, n=32; ≥2 HRCAs, n=13; total, n=111) and maintenance (0 HRCA, n=62; 1 HRCA, n=29; ≥2 HRCAs, n=10; total, n=101).
eDuration of study treatment is from initiation of therapy to completion of consolidation therapy, including ASCT.
Efficacy

Efficacy Outcomes by Cytogenetic Risk Statusin the GRIFFIN Studya,10
Parameter
Standard-Risk
0 HRCA (n=67)
High-Risk
1 HRCA (n=34)
Ultra-High-Risk
≥2 HRCAs (n=13)
≥CR,b %
90.9
78.8
61.5
24-month PFS rate, %
96.7
93.8
64.2
36-month PFS rate, %
96.7
90.5
53.5
48-month PFS rate, %
93.7
90.5
53.5
MRD negative
   Evaluable population, n
67c
34c
13c
      10-5 sensitivity, %
76.1
55.9
61.5
      10-6 sensitivity, %
44.8
26.5
15.4
   In patients achieving ≥CR, n
60
26
8
      10-5 sensitivity, %
83.3
69.2
87.5
Durable MRD-negativity lasting ≥12 months
   Evaluable population, n
67c
34c
13c
      10-5 sensitivity, %
53.7
38.2
30.8
MRD (10-5) conversion rate
   Evaluable population, n
67c
34c
13c
      MRD-positive by the end of
      induction and then became
      MRD-negative, %
49.3
41.2
38.5
      MRD-positive by the end of
      consolidation and then became
      MRD-negative, %
19.4
11.8
23.1
   Median time to MRD-negativity
   (10-5),c months
8.5
8.6
19.6
Abbreviations: ≥CR, complete response or better; HRCA, high-risk cytogenetic abnormality; MRD, minimal residual disease; PFS, progression-free survival.
aHRCAs include any of the following genetic abnormalities: del(17p), t(4;14), t(14;16), t(14;20), and gain/amp(1q21) (≥3 copies of chromosome 1q21). Patients were grouped into categories: standard risk (0 HRCA), high risk (1 HRCA), or ultra-high risk (≥2 HRCAs).
bEvaluable patients in GRIFFIN were the response-evaluable population (0 HRCA, n=66; 1 HRCA, n=33; ≥2 HRCAs, n=13).
cFor GRIFFIN, the D-R group included patients from the randomized phase (n=104) and the safety run-in phase (n=16). Patients were grouped by HRCA: 0 HRCA (n=67), 1 HRCA (n=34), or ≥2 HRCAs (n=13). 6 patients were not evaluable for cytogenetic abnormalities.
Safety
  • In the GRIFFIN study, 8 patients died while on D-VRd therapy (0 HRCA, n=2 [due to adverse event (bronchopneumonia) and PD]; 1 HRCA, n=1 [due to PD]; ≥2 HRCAs, n=4 [all due to PD]; not evaluable for cytogenetics, n=1 [due to respiratory failure]).

Post Hoc Analysis of the Incidence of VTE

Sborov et al (2022)11 conducted a post hoc analysis to evaluate the risk and incidence of VTE in patients receiving D-VRd vs VRd in the GRIFFIN study.

Study Design/Methods

  • The risk of VTE was assessed using the SAVED risk assessment model (<2 points, low risk; >2 points, high risk), as described below:
    • Surgery within 90 days (S; +2)
    • Asian race (A; -3)
    • History of VTE (V; +3)
    • Eighty (age ≥80 years; E; +1)
    • Dexamethasone dose (D; +2 for high, +1 for standard)
  • All patients received VTE prophylaxis with at least aspirin ≥162 mg/day. Patients with increased risk of VTE received prophylaxis with enoxaparin 40 mg/day SC or other low-molecular-weight heparin (LMWH) at an equivalent dose and frequency. Vitamin K antagonists, factor Xa inhibitors, or direct thrombin inhibitors could be used at treating physician's discretion.

Results

Patient Characteristics

Demographic and Baseline Disease Characteristics Among Patients Who Did or Did Not Experience VTEs11
Characteristic
Patients Who Experienced VTEs
Patients Who Did Not Experience VTEs
Total (n=26)
D-VRd (n=10)
VRd (n=16)
Total (n=181)
D-VRd (n=94)
VRd
(n=87)
Age, years
   Median (range)
57.5
(35-70)
54.0
(35-70)
59.5
(47-70)
60.0
(29-70)
59.5
(29-70)
61.0
(40-70)
   <65, n (%)
17 (65.4)
7 (70.0)
10 (62.5)
134 (74.0)
69 (73.4)
65 (74.7)
   ≥65, n (%)
9 (34.6)
3 (30.0)
6 (37.5)
47 (26.0)
25 (26.6)
22 (25.3)
Male, n (%)
19 (73.1)
8 (80.0)
11 (68.8)
99 (54.7)
50 (53.2)
49 (56.3)
Weight, kg
n=26
n=10
n=16
n=179
n=92
n=87
   Median (range)
87.1
(62.0-148.5)
81.9
(63.6-141.5)
88.2
(62.0-148.5)
80.4
(37.4-158.6)
78.9
(48.8-158.6)
82.7
(37.4-150.1)
ECOG PS score, n (%)
n=26
n=10
n=16
n=177
n=91
n=86
   0
3 (11.5)
1 (10.0)
2 (12.5)
76 (42.9)
38 (41.8)
38 (44.2)
   1
17 (65.4)
7 (70.0)
10 (62.5)
86 (48.6)
44 (48.4)
42 (48.8)
   2
6 (23.1)
2 (20.0)
4 (25.0)
15 (8.5)
9 (9.9)
6 (7.0)
ISS disease stage, n (%)a
   I
13 (50.0)
6 (60.0)
7 (43.8)
86 (47.5)
43 (45.7)
43 (49.4)
   II
13 (50.0)
4 (40.0)
9 (56.3)
64 (35.4)
36 (38.3)
28 (32.2)
   III
0
0
0
28 (15.5)
14 (14.9)
14 (16.1)
   Missing
0
0
0
3 (1.7)
1 (1.1)
2 (2.3)
Type of measurable disease, n (%)b
   Serum and urine
4 (15.4)
1 (10.0)
3 (18.8)
33 (18.2)
22 (23.4)
11 (12.6)
   Free light chain
3 (11.5)
2 (20.0)
1 (6.3)
23 (12.7)
13 (13.8)
10 (11.5)
   Serum only
14 (53.8)
4 (40.0)
10 (62.5)
99 (54.7)
49 (52.1)
50 (57.5)
   Urine only
5 (19.2)
3 (30.0)
2 (12.5)
22 (12.2)
9 (9.6)
13 (14.9)
   Not evaluable
0
0
0
4 (2.2)
1 (1.1)
3 (3.4)
Bone marrow involvement (% plasma cells, bone marrow biopsy/aspirate), n (%)c
   <10
3 (11.5)
1 (10.0)
2 (12.5)
13 (7.2)
9 (9.6)
4 (4.6)
   10-59
9 (34.6)
4 (40.0)
5 (31.3)
88 (48.6)
42 (44.7)
46 (52.9)
   ≥60
14 (53.8)
5 (50.0)
9 (56.3)
73 (40.3)
40 (42.6)
33 (37.9)
   Missing
0
0
0
7 (3.9)
3 (3.2)
4 (4.6)
Time from MM diagnosis to randomization
n=26
n=10
n=16
n=179
n=93
n=86
   Median (range),
   months
0.8 (0-3)
0.4 (0-3)
0.9 (0-2)
0.8 (0-61)
0.7 (0-12)
0.9 (0-61)
Cytogenetic profile, n (%)d
n=25
n=10
n=15
n=170
n=88
n=82
   Standard risk, n (%)
21 (84.0)
8 (80.0)
13 (86.7)
144 (84.7)
74 (84.1)
70 (85.4)
   High risk, n (%)
4 (16.0)
2 (20.0)
2 (13.3)
26 (15.3)
14 (15.9)
12 (14.6)
      del17p
4 (16.0)
2 (20.0)
2 (13.3)
10 (5.9)
6 (6.8)
4 (4.9)
      t(4;14)
1 (4.0)
0
1 (6.7)
13 (7.6)
8 (9.1)
5 (6.1)
      t(14;16)
0
0
0
4 (2.4)
1 (1.1)
3 (3.7)
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; Ig, immunoglobulin; ISS, International Staging System; MM, multiple myeloma; VRd, bortezomib + lenalidomide + dexamethasone; VTEs, vascular thrombotic events.
aBased on the combination of serum β2-microglobulin and albumin.
bIncludes IgD, IgM, IgE, and biclonal.
cHighest value by biopsy or aspirate.
dCytogenetic risk was based on local fluorescence in situ hybridization or karyotype analysis. Patients with high-risk cytogenetics had a del17p, t(4;14) or t(14;16) abnormality; a patient could be counted in more than 1 subcategory. Patients with standard-risk cytogenetic abnormalities had an absence of high-risk cytogenetic abnormalities.
Efficacy

Response Rates in Patients With VTE11
Parameter, %
D-VRd (n=10)
VRd (n=16)
End of Induction
End of ASCT
End of Consolidation
After 2 Years of Maintenance
End of Induction
End of ASCT
End of Consolidation
After 2 Years of Maintenance
≥CR
20.0
20.0
50.0
90.0
25.0
31.3
31.3
68.8
   sCR
10.0
10.0
40.0
70.0
18.8
25.0
25.0
56.3
   CR
10.0
10.0
10.0
20.0
6.3
6.3
6.3
12.5
VGPR
50.0
60.0
50.0
10.0
50.0
50.0
56.3
18.8
PR
30.0
20.0
-
-
25.0
18.8
12.5
12.5
Abbreviations: ASCT, autologous stem cell transplant; CR, complete response; ≥CR, complete response or better; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; PR, partial response; sCR, stringent complete response; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone; VTE, vascular thrombotic event.

Response Rates in Patients With VTE at the First Onset of VTE11
Parameter, %
D-VRd (n=10)
VRd (n=16)
≥CR
50.0
31.3
   sCR
30.0
25.0
   CR
20.0
6.3
VGPR
30.0
43.8
PR
20.0
12.5
SD/PD/NE
-
12.5
Abbreviations: CR, complete response; ≥CR, complete response or better; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; NE, not evaluable; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone; VTE, vascular thrombotic event.
Safety
  • In the D-VRd vs VRd arm, VTEs occurred in 10.1% (n=10) vs 15.7% (n=16) of patients in the safety analysis population. See Table: VTEs in the Safety Analysis Population.
  • The median time to first onset of VTE was 305 days (range, 6-810) in the D-VRd arm and 119 days (range, 21-822) in the VRd arm.
  • In the D-VRd vs VRd arm, new onset VTEs were reported at the following stages:
    • Induction (cycles 1-4): 5.1% (n=5) vs 8.8% (n=9)
    • Consolidation (cycles 5-6): 0% (n=0) vs 1.4% (n=1)
    • Maintenance:
      • Cycles 7-18: 2.2% (n=2) vs 7.0% (n=5)
      • Cycles 18+: 3.6% (n=3) vs 1.7% (n=1)
  • In the D-VRd vs VRd arm, the median SAVED score was 0 (range, 0 to 3) vs 0 (range, 3 to 4) in patients in the ITT population and 0 (range, 0-3) vs 0.5 (range, 0-4) in patients experiencing VTE.
  • The median number of cardiovascular comorbidities both in patients in the overall population and patients experiencing VTE was 1.
  • In the D-VRd vs VRd arm, antithrombosis prophylaxis at any time was received by 84.8% (n=84) vs 83.3% (n=85) of patients in the overall safety population and by 80.0% (n=8) vs 93.8% (n=15) of patients who developed VTE.
    • Overall, 60.0% (n=6) of patients in the D-VRd arm and 68.8% (n=11) of patients in the VRd arm were receiving antithrombosis prophylaxis during the first onset of VTE.

VTEs in the Safety Analysis Populationa,11
VTE, n (%)
D-VRd (n=99)
VRd (n=102)
Grade 1
Grade 2-4
Total
Grade 1
Grade 2-4
Total
Total number with ≥1 VTE
1 (1.0)
9 (9.1)
10 (10.1)
1 (1.0)
15 (14.7)
16 (15.7)
Embolic and thrombotic events
2 (2.0)
3 (3.0)
5 (5.1)
1 (1.0)
10 (9.8)
11 (10.8)
   Deep vein thrombosis
1 (1.0)
1 (1.0)
2 (2.0)
0
7 (6.9)
7 (6.9)
   Pulmonary embolism
0
2 (2.0)
2 (2.0)
0
4 (3.9)
4 (3.9)
   Embolism venous
0
0
0
1 (1.0)
0
1 (1.0)
   Jugular vein thrombosis
0
1 (1.0)
1 (1.0)
0
1 (1.0)
1 (1.0)
   Subclavian vein thrombosis
0
1 (1.0)
1 (1.0)
0
0
0
   Thrombophlebitis superficial
1 (1.0)
1 (1.0)
2 (2.0)
0
0
0
Unspecified and mixed arterial and venous
0
6 (6.1)
6 (6.1)
1 (1.0)
5 (4.9)
6 (5.9)
   Embolism
0
2 (2.0)
2 (2.0)
1 (1.0)
2 (2.0)
3 (2.9)
   Cerebral congestion
0
2 (2.0)
2 (2.0)
0
1 (1.0)
1 (1.0)
   Cerebrovascular accident
0
0
0
0
1 (1.0)
1 (1.0)
   Hemiparesis
0
0
0
0
1 (1.0)
1 (1.0)
   Intestinal infarction
0
1 (1.0)
1 (1.0)
0
0
0
   Vascular access site
   thrombosis
0
1 (1.0)
1 (1.0)
0
0
0
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; VRd, bortezomib + lenalidomide + dexamethasone; VTE, vascular thrombotic event.
aNo grade 5 VTEs were reported in either treatment arm.

PROs in the GRIFFIN Study

Silbermann et al (2024)13 reported PROs from GRIFFIN at the final study analysis (median follow-up, 49.6 months) following ≥1 year of follow-up, death, or withdrawal from the study for all patients.

Study Design/Methods

  • PROs were assessed using the following questionnaires, and the scores were derived using scales ranging from 0 to 10013:
    • EORTC QLQ-C30
      • Five functional scales: physical, role, emotional, cognitive, and social
      • Three symptom scales: pain, fatigue, and nausea and vomiting
      • Six single items: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties
    • EORTC QLQ-MY20
      • Two symptom scales: disease symptoms and treatment side effects
      • One functional scale: future perspective
      • One single item: body image
    • EQ-5D-5L
      • Five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression
      • VAS, ranging from “the worst health you can imagine” (0) to “the best health you can imagine” (100)
      • Utility score based on 5 dimensions
  • PROs were assessed by completing electronic or paper-based questionnaires on day 1 of cycles 1, 2, and 3 and on day 21 of cycle 4 (end of induction therapy); on day 1 of cycle 5 and C6D21 (end of posttransplant consolidation therapy); and at months 6, 12, 18, and 24 of maintenance therapy.13
  • For the EORTC QLQ-C30 and EORTC QLQ-MY20 scales, higher scores indicate improved health-related quality of life (HRQoL) and functioning on GHS, functional scales, and body image but more/worsening on symptom scales.13
  • For EQ-5D-5L, higher scores on VAS represent a better HRQoL.13

Results

Patient Characteristics
  • A total of 207 patients were randomized 1:1 to receive D-VRd (n=104) or VRd (n=103).13
  • The median follow-up was 49.6 months.13
  • Compliance rates for completing the PRO questionnaires were as follows13:
    • At baseline: D-VRd, 85%; VRd, 82%
    • At C6D21: D-VRd, 63%; VRd, 49%
    • At month 24 (M24): D-VRd, 49%; VRd, 45%
  • Baseline PRO scores were comparable between the D-VRd and VRd groups and are summarized in Table: Baseline PRO Instrument Scores.13

Baseline Demographics and Clinical Characteristics13
Characteristic
D-VRd
(n=104)
VRd
(n=103)
Median (range), years
59 (29-70)
61 (40-70)
   <65, n (%)
76 (73.1)
75 (72.8)
   ≥65, n (%)
28 (26.9)
28 (27.2)
Sex, n (%)
   Male
58 (55.8)
60 (58.3)
   Female
46 (44.2)
43 (41.7)
Race, n (%)
n=103
n=103
   Asian
0
2 (1.9)
   Black or African American
14 (13.6)
18 (17.5)
   White
85 (82.5)
76 (73.8)
   Other
2 (1.9)
1 (1.0)
   Multiple
0
1 (1.0)
   Unknown
2 (1.9)
5 (4.9)
Ethnicity, n (%)
   Hispanic or Latino
9 (8.7)
6 (5.8)
   Not Hispanic or Latino
92 (88.5)
93 (90.3)
   Not reported
1 (1.0)
3 (2.9)
   Unknown
2 (1.9)
1 (1.0)
ECOG PS score, n (%)a
n=101
n=102
   0
39 (38.6)
40 (39.2)
   1
51 (50.5)
52 (51.0)
   2
11 (10.9)
10 (9.8)
ISS disease stage, n (%)b
   I
49 (47.1)
50 (48.5)
   II
40 (38.5)
37 (35.9)
   III
14 (13.5)
14 (13.6)
   Missing
1 (1.0)
2 (1.9)
Baseline creatinine clearance, mL/min, n (%)
   30-50
9 (8.7)
9 (8.7)
   >50
95 (91.3)
94 (91.3)
Cytogenetic risk profile, n (%)c
n=98
n=97
   Standard risk
82 (83.7)
83 (85.6)
   High risk
16 (16.3)
14 (14.4)
Time since diagnosis of MM, months
n=103
n=102
   Median (range)
0.7 (0-12)
0.9 (0-61)
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; MM, multiple myeloma; VRd, bortezomib + lenalidomide + dexamethasone.
a ECOG PS is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bThe ISS disease stage is based on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease.
cCytogenetic risk was assessed by fluorescence in situ hybridization (local testing); high risk was defined as the presence of del(17p), t(4;14), or t(14;16) among patients with available cytogenetic risk data.

Baseline PRO Instrument Scores13
PRO Score
D-VRd
(n=88)
VRd
(n=84)
EORTC QLQ-C30 score, mean (SD)
   GHS
63.2 (24.3)
65.1 (21.8)
   Functional scales
      Physical functioning
70.9 (27.2)
72.5 (24.8)
      Role functioning
61.7 (34.6)
65.9 (32.4)
      Emotional functioning
74.4 (21.5)
73.7 (23.0)
      Cognitive functioning
79.9 (27.8)
82.5 (22.7)
      Social functioning
67.1 (30.2)
73.0 (28.9)
   Symptom scales
      Pain
44.1 (34.5)
43.5 (33.4)
      Fatigue
39.9 (30.8)
36.1 (26.2)
      Nausea and vomiting
7.0 (12.3)
3.6 (10.0)
EORTC QLQ-MY20 score, mean (SD)
   Future perspective
52.7 (26.0)
58.2 (25.1)
   Body image
75.4 (32.2)
81.4 (28.0)
   Disease symptoms
34.3 (24.9)
31.2 (20.9)
   Treatment side effects
18.7 (17.9)
15.3 (14.5)
EQ-5D-5L score, mean (SD)
   VAS
68.0 (21.0)
68.5 (20.0)
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item; EORTC QLQ-MY20, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma Module 20-item; EQ-5D-5L, EuroQol 5-dimensional descriptive system; GHS, global health status; PRO, patient-reported outcome; SD, standard deviation; VAS, visual analog scale; VRd, bortezomib + lenalidomide + dexamethasone.
EORTC QLQ-C30 GHS and Functional Scores
  • During the induction phase (cycles 1-4), no meaningful changes were observed in the GHS score in either the D-VRd or VRd group. On C6D21 and during maintenance treatment, a greater least squares (LS) mean change from baseline was observed.13
  • During the consolidation phase, a similar improvement was noted in the LS mean change from baseline in physical functioning scores in the D-VRd and VRd groups.13
  • A substantial improvement was observed in the LS mean change from baseline in role functioning scores in the D-VRd and VRd groups during the consolidation and maintenance phases.13
  • No meaningful LS mean change from baseline was observed in emotional functioning scores throughout the induction phase (cycles 1-4), but the improvement in baseline scores was comparable at C6D21 and throughout the maintenance phase between the D-VRd and VRd groups.13
  • In the D-VRd and VRd groups, no meaningful LS mean change from baseline was observed in cognitive functioning scores.13
  • During the consolidation phase and at M24, an improvement in the LS mean change from baseline in social functioning scores was observed in the D-VRd and VRd groups.13
EORTC QLQ-C30 Symptom Scales
  • A higher reduction in pain symptoms was observed in the D-VRd group than that in the VRd group. A greater than 20-point change on average was seen after consolidation,
  • which was sustained throughout the maintenance phase.13
  • Patients experienced a reduction in fatigue symptoms from baseline for all time points with D-VRd treatment and from the start of posttransplant consolidation (cycle 5 day 1) with VRd treatment.13
  • In the D-VRd and VRd groups, no meaningful LS mean change from baseline was observed in nausea and vomiting scores.13
EORTC QLQ-C30 6 Single Items
  • In the D-VRd vs VRd group, respectively, the mean baseline values for the 6 single items were as follows: dyspnea, 14.4 vs 13.1; sleep disturbance, 35.6 vs 31.4; appetite loss, 20.1 vs 21.4; constipation, 19.3 vs 14.3; diarrhea, 6.4 vs 5.6; and financial difficulties, 25.3 vs 23.8.13
EORTC QLQ-MY20 Scales
  • At all time points, the improvement from baseline in future perspective scores was comparable between the D-VRd and VRd groups.13
  • During the induction and consolidation phases, the change from baseline in body image score was comparable between the D-VRd and VRd groups.13
    • During maintenance months 6, 12, and 18, a greater change from baseline in body image was observed in the D-VRd group than in the VRd group.
  • In the D-VRd and VRd groups, a reduction in disease symptom score was observed during consolidation, with further reduction observed at the end of maintenance.13
  • The LS mean change from baseline in treatment side effects favored D-VRd over VRd during the maintenance phase.13
EQ-5D-5L VAS
  • In the D-VRd and VRd groups, the improvement from baseline on EQ-5D-5L VAS was comparable across all time points after induction.13
Improvement and Worsening of PRO Scores

Time to Improvement of EORTC QLQ-C30, EORTC QLQ-MY20, and EQ-5D-5L Scores24
PRO Scores
Time to Improvement
D-VRd
(n=104)
Median (Range), Months
VRd
(n=103)
Median (Range), Months
EORTC QLQ-C30, n (%)
   GHS
55 (52.9)
6.3 (0.7-38.2)
46 (44.7)
1.6 (0.4-48.0)
   Functional scales
      Physical functioning
49 (47.1)
1.5 (0.7-35.3)
46 (44.7)
1.4 (0.7-46.2)
      Role functioning
44 (42.3)
3.3 (0.7-31.9)
35 (34.0)
1.7 (0.7-30.7)
      Emotional functioning
51 (49.0)
1.5 (0.7-45.0)
38 (36.9)
0.8 (0.5-41.0)
      Cognitive functioning
36 (34.6)
0.8 (0.7-24.3)
37 (35.9)
0.8 (0.7-33.6)
      Social functioning
53 (51.0)
1.5 (0.7-20.3)
41 (39.8)
1.5 (0.4-34.6)
   Symptom scales
      Pain
54 (51.9)
1.5 (0.7-48.3)
38 (36.9)
1.4 (0.5-45.0)
      Fatigue
48 (46.2)
2.6 (0.7-35.2)
37 (35.9)
2.9 (0.5-29.2)
      Nausea and vomiting
26 (25.0)
0.9 (0.7-33.7)
11 (10.7)
0.8 (0.7-8.2)
EORTC QLQ-MY20, n (%)
   Future perspective
60 (57.7)
1.5 (0.7-30.0)
51 (49.5)
1.5 (0.4-27.0)
   Body image
37 (35.6)
1.4 (0.7-51.4)
25 (24.3)
1.3 (0.7-26.2)
   Disease symptoms
54 (51.9)
1.0 (0.7-39.4)
46 (44.7)
1.6 (0.7-34.6)
   Treatment side effects
35 (33.7)
2.4 (0.7-34.2)
20 (19.4)
1.6 (0.7-45.2)
EQ-5D-5L, n (%)
   VAS
51 (49.0)
1.5 (0.7-36.4)
49 (47.6)
1.7 (0.7-42.9)
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item; EORTC QLQ-MY20, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma Module 20-item; EQ-5D-5L, EuroQol 5-dimensional descriptive system; GHS, global health status; PRO, patient-reported outcome; VAS, visual analog scale; VRd, bortezomib + lenalidomide + dexamethasone.

Proportion of Patients With Clinically Meaningful Improvement and Worsening of PRO Scores From Baseline at Time Point24
PRO Scores, %
Improvement
Worsening
End of
Consolidation
(%)
Maintenance
Month 24
(%)
End of
Consolidation
(%)
Maintenance
Month 24
(%)
D-VRd
(n=50)
VRd
(n=31)
D-VRd
(n=39)
VRd
(n=19)
D-VRd
(n=50)
VRd
(n=31)
D-VRd
(n=39)
VRd
(n=19)
EORTC QLQ-C30
   GHS
62.0
54.8
61.5
47.4
30.0
29.0
15.4
42.1
   Functional scales
      Physical functioning
44.0
51.6
61.5
47.4
14.0
22.6
5.1
21.1
      Role functioning
58.0
22.6
56.4
42.1
22.0
32.3
12.8
26.3
      Emotional functioning
32.0
41.9
46.2
52.6
10.0
9.7
7.7
15.8
      Cognitive functioning
34.0
22.6
35.9
26.3
34.0
45.2
20.5
36.8
      Social functioning
48.0
25.8
59.0
26.3
26.0
25.8
15.4
21.1
   Symptom scales
      Pain
66.0
58.1
74.4
57.9
8.0
12.9
7.7
15.8
      Fatigue
54.0
41.9
71.8
47.4
28.0
22.6
12.8
31.6
      Nausea and vomiting
24.0
16.1
30.8
15.8
12.0
19.4
15.4
26.3
EORTC QLQ-MY20
   Future perspective
66.0
61.3
76.9
68.4
18.0
19.4
7.7
15.8
   Body image
28.0
12.9
33.3
31.6
32.0
25.8
15.4
26.3
   Disease symptoms
64.0
61.3
53.8
42.1
10.0
9.7
7.7
26.3
   Treatment side effects
22.0
9.7
35.9
26.3
30.0
41.9
5.1
21.1
EQ-5D-5L
   VAS
62.0
58.1
56.4
36.8
8.0
16.1
12.8
26.3
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item; EORTC QLQ-MY20, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma Module 20-item; EQ-5D-5L, EuroQol 5-dimensional descriptive system; GHS, global health status; PRO, patient-reported outcome; VAS, visual analog scale; VRd, bortezomib + lenalidomide + dexamethasone.

Median Time to Worsening from Baseline of PRO Scores13,24 
PRO Score
Median Time to Worseninga from Baseline (Months)
D-VRd
(n=104)
VRd
(n=103)
HR
(95% CI)
EORTC QLQ-C30
   GHS
45.2
14.4
0.71 (0.46-1.10)
   Functional scales
      Physical functioning
31.3
24.0
0.84 (0.55-1.30)
      Role functioning
NR
36.4
0.82 (0.51-1.31)
      Emotional functioning
40.1
35.3
0.85 (0.54-1.36)
      Cognitive functioning
8.1
8.6
0.91 (0.61-1.35)
      Social functioning
2.8
3.0
1.05 (0.71-1.55)
   Symptom scales
      Pain
NR
NR
0.71 (0.40-1.26)
      Fatigue
24.6
30.8
0.97 (0.63-1.48)
      Nausea and vomiting
33.0
7.2
0.88 (0.58-1.34)
EORTC QLQ-MY20
   Future perspective
34.7
30.8
0.95 (0.50-1.82)
   Body image
8.5
8.9
0.96 (0.64-1.44)
   Disease symptoms
NR
44.7
0.75 (0.43-1.30)
   Treatment side effects
6.9
2.6
0.82 (0.57-1.18)
EQ-5D-5L
   VAS
33.9
32.0
0.86 (0.56-1.33)
Abbreviations: CI, confidence interval; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item; EORTC QLQ-MY20, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma Module 20-item; EQ-5D-5L, EuroQol 5-dimensional descriptive system; GHS, global health status; HR, hazard ratio; NR, not reached; PRO, patient-reported outcome; VAS, visual analog scale; VRd, bortezomib + lenalidomide + dexamethasone.
aWorsening was defined as an increase in symptom scores or a decrease in other scores that was at least half of the standard deviation from baseline values, with standard deviation calculated from scores at baseline combining both treatment groups.

Stem Cell Collection in the GRIFFIN Study

Chhabra et al (2023)14 conducted a post hoc analysis evaluating the patient characteristics, stem cell mobilization and yields, and transplant outcomes following frontline DARZALEX-based induction therapy in the MASTER and GRIFFIN studies. Results specific to the GRIFFIN study have been summarized below.

Results

Patient Characteristics
  • Among the 207 patients randomized in the GRIFFIN study, 95/104 (91%) patients in the D-VRd arm and 80/103 (78%) patients in the VRd arm underwent stem cell mobilization. Among the mobilized patients, 99% (94 of 95) in the D-VRd arm and 98% (78 of 80) in the VRd arm underwent ASCT.
  • The median duration of follow-up was 38.6 months.
  • The baseline patient demographics and clinical characteristics are summarized in Table: Baseline Characteristics in the GRIFFIN Study.

Baseline Characteristics in the GRIFFIN Study14
Characteristic
D-VRd
VRd
All Patients
Received Upfront Plerixafor
Rescue Plerixafor Strategy (n=46)a
All Patients
Received Upfront Plerixafor
Rescue Plerixafor Strategy (n=49)a
Received Rescue Plerixafor
Received G-CSF Only
Received Rescue Plerixafor
Received G-CSF Only
Patients who underwent mobilization, n
95
49
19
19
80
31
13
28
Age, years
   Median (range)
59
(29-70)
60
(29-70)
55
(35-70)
58
(34-70)
59
(40-70)
59
(47-70)
62
(49-69)
61
(40-68)
   <65, n (%)
69 (73)
37 (76)
12 (63)
12 (63)
60 (75)
24 (77)
7 (54)
21 (75)
   ≥65, n (%)
26 (27)
12 (24)
7 (37)
7 (37)
20 (25)
7 (23)
6 (46)
7 (25)
Male, n (%)
51 (54)
28 (57)
8 (42)
12 (63)
43 (54)
14 (45)
6 (46)
17 (61)
ISS disease stage, n (%)b
   I
46 (48)
22 (45)
10 (53)
10 (53)
38 (48)
16 (52)
4 (31)
13 (46)
   II
36 (38)
19 (39)
6 (32)
8 (42)
29 (36)
9 (29)
7 (54)
11 (39)
   II
13 (14)
8 (16)
3 (16)
1 (5)
12 (15)
5 (16)
2 (15)
4 (14)
   Missing
0
0
0
0
1 (1)
1 (3)
0
0
Cytogenetic risk, n (%)c
n=91
n=47
n=18
n=18
n=77
n=29
n=13
n=28
   Standard risk
75 (82)
38 (81)
13 (72)
18 (100)
66 (86)
24 (83)
12 (92)
23 (82)
   High risk
16 (18)
9 (19)
5 (28)
0
11 (14)
5 (17)
1 (8)
5 (18)
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; G-CSF, granulocyte colony-stimulating factor; ISS, International Staging System; VRd, bortezomib + lenalidomide + dexamethasone.
aAmong the mobilized patients in GRIFFIN, 9 (D-VRd, n=5; VRd, n=4) patients received cyclophosphamide, and no accurate information on mobilization regimen used was available for 16 (D-VRd, n=8; VRd, n=8) patients.
bISS staging is based on the combination of serum β2-microglobulin and albumin. Higher stages indicate more advanced disease.
cCytogenetic risk was assessed by fluorescence in situ hybridization (local testing); high cytogenetic risk was defined as the presence of del17p, t(4;14), or t(14;16) among patients with available cytogenetic risk data.
Summary of ASCT
  • A higher rate of mobilization was observed in the D-VRd vs Rd arm due to lower rates of discontinuation during induction (D-VRd, 2%; VRd, 7%) and following induction but before mobilization (D-VRd, 3%; VRd, 14%).
  • A total of 68 (72%) patients in the D-VRd arm and 44 (55%) in the VRd arm received plerixafor either upfront or as a rescue strategy.
  • A total of 5 patients in the D-VRd arm and 4 in the VRd arm received cyclophosphamide.
  • A total of 19 (20%) patients in the D-VRd arm and 28 (35%) in the VRd arm received granulocyte colony-stimulating factor (G-CSF) alone.
  • The median CD34+ stem cell yield was 8.3×106 cells/kg in the D-VRd arm and 9.4×106 cells/kg in the VRd arm. In both arms, a numerically higher stem cell yield was reported in patients who received upfront plerixafor vs those who received rescue plerixafor (D-VRd, 8.8×106 cells/kg vs 7.1×106 cells/kg, P=0.10; VRd, 10.5×106 cells/kg vs 9.4×106 cells/kg, P=0.20; respectively).
  • Median number of days for stem cell collection was 2 in patients in the D-VRd arm and 1 in the VRd arm.
  • Additional data stratified by upfront plerixafor use, rescue plerixafor use, and G-CSF only use are summarized in Table: Summary of ASCT in the GRIFFIN Study.

Summary of ASCT in the GRIFFIN Studya,14
Parameter
All Patients
Received Upfront Plerixafor
Rescue Plerixafor Strategyb
Received Rescue Plerixafor
Received G-CSF Only
D-VRd
VRd
D-VRd
VRd
D-VRd
VRd
D-VRd
VRd
Pts who underwent
mobilization, n
95
80
49
31
19
13
19
28
Pts who received plerixafor, n
68
44
49
31
19
13
0
0
Mobilization attempts, n (%)
   1
89 (94)
74 (93)
46 (94)
28 (90)
19 (100)
12 (92)
17 (89)
27 (96)
   2
2 (2)
3 (4)
1 (2)
1 (3)
0
1 (8)
1 (5)
1 (4)
   3
0
1 (1)
0
0
0
0
0
0
   4
0
1 (1)
0
1 (3)
0
0
0
0
   Missing
4 (4)
1 (1)
2 (4)
1 (3)
0
0
1 (5)
0
Median stem cell collection target per ASCT (range), ×106 CD34+ cells/kg
2.5
(2-4)
2.5
(2-5)
2.5
(2-4)
2.5
(2-5)
2
(2-4)
2.5
(2-4)
2
(2-3)
2
(2-4)
Median duration of stem cell collection (range), days
2
(1-4)
1
(1-4)
2
(1-4)
1
(1-4)
1
(1-3)
2
(1-4)
2
(1-4)
1
(1-4)
Median stem cell yield (range), ×106 CD34+ cells/kg
8.3
(2.6-33)
9.4
(4.1-28.7)
8.8
(2.6-33)
10.5
(5.5-22.5)
7.1
(4.2-16.7)
9.4
(4.4-17.3)
8.3
(4.4-18.6)
7.6
(4.1-23)
Pts who collected the minimum threshold for ASCT, n (%)
89 (94)
79 (99)
45 (92)
30 (97)
19 (100)
13 (100)
18 (95)
28 (100)
Pts who collected 2x the minimum threshold for
ASCT, n (%)
81 (85)
74 (93)
42 (86)
29 (94)
16 (84)
11 (85)
17 (89)
26 (93)
Number of CD34+ cells transplanted (106 cells/kg),
median (range)
4.2
(2-27.6)
4.8
(1.1-15)
4.3
(2.5-27.6)
4.8
(1.1-15)
4.0
(2.0-8.3)
4.7
(1.7-12.2)
4.3
(2.8-9.3)
4.4
(2.0-13.2)
Median duration from end of induction to
apheresis (range), days
27
(0-63)
24
(4-133)
23
(14-48)
25.5
(4-133)
26
(0-36)
23
(14-43)
33
(13-63)
22.5
(12-55)
Pts who completed ASCT, n (%)
94 (99)
78 (98)
49 (100)
31 (100)
18 (95)
13 (100)
19 (100)
26 (93)
Abbreviations: ASCT, autologous stem cell transplant; CD34+, cluster of differentiation 34 positive; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; G-CSF, granulocyte colony-stimulating factor; pts, patients; VRd, bortezomib + lenalidomide + dexamethasone.
aAmong the mobilized patients in GRIFFIN, 9 (D-VRd, n=5; VRd, n=4) patients received cyclophosphamide, and no accurate information on mobilization regimen used was available for 16 (D-VRd, n=8; VRd, n=8) patients.
bPatients who did not receive upfront plerixafor had the treatment plan called “rescue plerixafor strategy.” Rescue plerixafor use was defined as only using plerixafor when deemed necessary “just-in-time” based on pre-apheresis blood CD34+ cell count after G-CSF. Patients in the rescue plerixafor strategy group did not receive upfront plerixafor, but received either rescue plerixafor or no plerixafor at all.

Post hoc Analysis of Patients Aged ≥65 Years From the PERSEUS and GRIFFIN Studies

Rodriguez-Otero et al (2025)15 presented results from a post hoc, pooled analysis of data from the PERSEUS and GRIFFIN studies that evaluated the efficacy and safety of DARZALEX FASPRO or DARZALEX, respectively in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) vs VRd in patients aged ≥65 years.

Results

Patient Characteristics

  • Patients aged ≥65 years represented 25.5% of patients in the PERSEUS study (D-VRd, 94 of 355 patients vs VRd, 87 of 354 patients) and 27.1% of patients in the GRIFFIN study (D-VRd, 28 of 104 patients vs VRd, 28 of 103 patients).15 The baseline demographic and disease characteristics are summarized in Table: Baseline Demographic and Disease Characteristics in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN ITT Population.
  • The median duration of treatment for patients aged ≥65 years was 37.4 months (range, 0.5-52.5) and 32.6 months (range, 0.1-53.0) in the D-VRd and VRd groups, respectively.
  • The median number of treatment cycles received in the D-VRd vs VRd group were 33.5 vs 31.0 cycles.
  • The median relative dose intensities were similar between the D-VRd vs VRd group for bortezomib (92.9% vs 93.5%, respectively) and dexamethasone (95.5% vs 100%, respectively) but were slightly lower in the D-VRd group for lenalidomide (75.5% vs 87.7%, respectively). The median relative dose intensity for DARZALEX FASPRO/DARZALEX in the D-VRd group was 99.7%.
  • Cycle delays were reported in the D-VRd vs VRd group for 82.5% vs 75.4% of patients, respectively.
  • Treatment discontinuation rates in the D-VRd vs VRd group were higher for lenalidomide (23.3% vs 17.5%, respectively) but were comparable between the D-VRd vs VRd group for bortezomib (12.5% vs 12.3%, respectively) and dexamethasone (3.3% vs 3.5%, respectively).
  • The discontinuation rate of DARZALEX FASPRO/DARZALEX in the D-VRd group was 2.5%.

Baseline Demographic and Disease Characteristics in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN ITT Populationa,15
Characteristic
D-VRd
(n=122)
VRd
(n=115)
Median age (range), years
67 (65-70)
67 (65-70)
Sex, n (%)
   Female
46 (37.7)
48 (41.7)
   Male
76 (62.3)
67 (58.3)
Race, n (%)
   White
110 (90.2)
106 (92.2)
   Asian
4 (3.3)
1 (0.9)
   Black
2 (1.6)
3 (2.6)
   American Indian/Alaska Native
1 (0.8)
0
   Native Hawaiian/Pacific Islander
1 (0.8)
0
   Multiple/unknown/not reported
4 (3.3)
5 (4.3)
ECOG PS score, n/N (%)
   0
66/122 (54.1)
66/114 (57.9)
   1
47/122 (38.5)
40/114 (35.1)
   2
9/122 (7.4)
8/114 (7.0)
   3
0
0
ISS disease stageb, n (%)
   I
51 (41.8)
39 (33.9)
   II
32 (26.2)
33 (28.7)
   III
11 (9.0)
15 (13.0)
Type of measurable diseasec, n (%)
   Serum
96 (78.7)
100 (87.0)
      IgG
67 (54.9)
65 (56.5)
      IgA
24 (19.7)
28 (24.3)
      Otherd
5 (4.1)
7 (6.1)
   Urine only
13 (10.7)
9 (7.8)
   Serum FLC only
12 (9.8)
6 (5.2)
   Not evaluablee
1 (0.8)
0
Cytogenetic riskf, n/N (%)
   Standard risk
88/119 (73.9)
91/114 (79.8)
   High risk
27/119 (22.7)
22/114 (19.3)
      del(17p)
17/119 (14.3)
12/114 (10.5)
      t(4;14)
10/119 (8.4)
7/114 (6.1)
      t(14;16)
2/119 (1.7)
5/114 (4.4)
      Indeterminate
4/119 (3.4)
1/114 (0.9)
Abbreviations: D-VRd, DARZALEX FASPRO/DARZALEX + bortezomib, lenalidomide, and dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FLC, free-light chain; IgA/IgD/IgE/IgG/IgM, immunoglobulin A/D/E/G/M; ISS, International Staging System; ITT, intent-to-treat; VRd, bortezomib, lenalidomide, and dexamethasone.
aThe pooled ITT population included all patients aged ≥65 years who were randomized in PERSEUS or GRIFFIN.
bISS staging is derived based on the combination of serum β2-microglobulin and albumin.
cIncludes patients without measurable disease in serum and urine.
dIncludes patients with IgD, IgM, IgE, and biclonal disease.
eOne patient with no evaluable measurable disease.
fHigh risk was defined as ≥1 of the following cytogenetic abnormalities: del(17p), t(4;14), and/or t(14;16) by fluorescence in situ hybridization. Standard risk was defined by the absence of these cytogenetic abnormalities.
Transplant Characteristics
  • Among patients aged ≥65 years who received ≥1 dose of the study treatment, 93.3% (112/120) vs 84.2% (96/114) patients in the D-VRd vs VRd group, proceeded for stem cell mobilization.15
    • The median number of CD34+ cells collected was sufficient for transplant in both the treatment groups.
    • Two patients from the D-VRd group vs 1 patient from the VRd group had <2×106/kg CD34+ stem cells collected.
  • The proportions of patients who proceeded to transplant were comparable between the treatment groups (D-VRd, 86.7% vs VRd, 82.5%).15
    • The median time to engraftment was 14 (range, 0-33) days vs 13 (range, 1-48) days in the D-VRd vs VRD groups, respectively.
  • The stem cell mobilization and transplant outcomes are summarized in Table: Stem Cell Mobilization and Transplant Outcomes in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN Safety Population

Stem Cell Mobilization and Transplant Outcomes in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN Safety Populationa,15
Characteristic
D-VRd
(n=120)
VRd
(n=114)
Patients proceeded to stem cell mobilization, n (%)
112 (93.3)
96 (84.2)
Mobilization medication/therapy used, n (%)
   N
112
96
   G-CSFb
110 (98.2)
91 (94.8)
   Cyclophosphamide
71 (63.4)
51 (53.1)
   Plerixafor
59 (52.7)
32 (33.3)
   Chemotherapy
2 (1.8)
0 (0)
   Other
1 (0.9)
2 (2.1)
Patients with stem cells collected, n (%)
108 (90.0)
95 (83.3)
Total number of CD34+ stem cells collected
   Median (range),×106/kg
4.22 (1.80-13.50)
5.76 (1.12-49.50)
   <2×106/kg, n (%)
2 (1.9)
1 (1.1)
   2 to <5×106/kg, n (%)
68 (63.0)
35 (36.8)
   ≥5×106/kg, n (%)
38 (35.2)
59 (62.1)
Patients who completed stem cell conditioning therapy, n (%)
104 (86.7)
94 (82.5)
Total dose of melphalan conditioning therapy
   N
102
94
   Median (range), mg/m2
193 (59-385)
192 (52-371)
Patients who proceeded to ASCT, n (%)
104 (86.7)
94 (82.5)
Time to achieve ANC ≥0.5×109/L, post-transplant
   N
103
93
   Median (range), days
13 (0-28)
12 (0-34)
Time to achieve platelets ≥20×109/L post-transplant without transfusionc
   N
103
93
   Median (range), days
13 (0-33)
12 (1-48)
Time to engraftmentc,d
N
103
93
Median (range), days
14 (0-33)
13 (1-48)
Abbreviations: ANC, absolute neutrophil count; ASCT, autologous stem cell transplant; CD, cluster of differentiation; D-VRd, DARZALEX FASPRO/DARZALEX + bortezomib, lenalidomide, and dexamethasone; G-CSF, granulocyte colony-stimulating factor; VRd, bortezomib, lenalidomide, and dexamethasone.
aPooled safety population included all patients aged ≥65 years who were randomized in PERSEUS or GRIFFIN and received ≥1 dose of study treatment.
bIncluded standardized medications of filgrastim, lenograstim, and G-CSF.
cNumber of days from the transplant date, excluding patients whose counts did not reach nadir below the set threshold.
dThe date of engraftment after transplant was defined as the latest date of ANC ≥0.5×109/L and platelet count ≥20×109/L. Patients with hematopoietic reconstitution were included.
Efficacy

Response Rates, Overall and Sustained MRD-Negativity Rates in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN ITT Populationa,15
Parameter
D-VRd
(n=122)
VRd
(n=115)
OR
(95% CI)b
P Valuec
n (%)
95% CI
n (%)
95% CI
≥CR
101
(82.8)
74.9-89.0
77
(67.0)
57.6-75.4
2.37
(1.28-4.39)
0.005
≥VGPR
114
(93.4)
87.5-97.1
99
(86.1)
78.4-91.8
2.47
(1.03-5.92)
0.04
ORRd
116
(95.1)
89.6-98.2
110
(95.7)
90.1-98.6
0.86
(0.25-2.96)
0.81
Best response
   sCR
72
(59.0)
49.7-67.8
57
(49.6)
40.1-59.0
1.49
(0.88-2.53)
0.14
   CR
29
(23.8)
16.5-32.3
20
(17.4)
11.0-25.6
-
-
   VGPR
13
(10.7)
5.8-17.5
22
(19.1)
12.4-27.5
-
-
   PR
2
(1.6)
0.2-5.8
11
(9.6)
4.9-16.5
-
-
   SD
3
(2.5)
0.5-7.0
2
(1.7)
0.2-6.1
-
-
   PD
0
NE-NE
0
NE-NE
-
   NE
3
(2.5)
0.5-7.0
3
(2.6)
0.5-7.4
-
Overall MRD-negativity (10-5), %
81
66.4)
-
48
(41.7)
-
2.75
(1.61-4.71)
0.0002
MRD-negativity (10-5) at the end of consolidation, %
60
(49.2)
-
34
29.6)
-
2.23
(1.31-3.80)
0.003
Sustained MRD-negativity (10-5) (≥12 months), %
64
(52.5)
-
30
26.1)
-
3.2
(1.83-5.58)
<0.0001
Abbreviations: CI, confidence interval; CR, complete response; D-VRd, DARZALEX FASPRO/DARZALEX + bortezomib + lenalidomide + dexamethasone; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; ORR, overall response rate; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone.
aPooled ITT population included all patients aged ≥65 years who were randomized in PERSEUS or GRIFFIN.
bMantel-Haenszel estimates of the common ORs for stratified tables were used. The stratification factors were ISS disease stage (I vs II vs III) and cytogenetic risk (high risk vs standard/unknown risk).
cP value from the stratified Cochran-Mantel-Haenszel chi-square test.
dORR was defined as sCR + CR + VGPR + PR.
Safety
  • The incidence of grade 3/4 TEAEs in the D-VRd vs VRd group among patients aged ≥65 years was 94.2% vs 86.8%, respectively.15
    • The incidence of serious TEAEs in the D-VRd vs VRd group among patients aged ≥65 years was 67.5% vs 52.6%, respectively.
  • A higher incidence of grade 3/4 infections of 36.3% vs 24.8% was observed in patients aged ≥65 years in the D-VRd vs VRd group, respectively.15
  • The percentage of patients with TEAEs that resulted in the discontinuation of ≥1 study drug in the D-VRd vs VRd group was 40.8% vs 45.6%, respectively, in patients aged ≥65 years. The summary of the most common TEAEs is presented in Table: Most Common TEAEs in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN Safety Population.
  • Treatment discontinuation was mostly due to peripheral sensory neuropathy: D-VRd, 12.5%; VRd, 13.2%.15

Most Common TEAEs in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN Safety Populationa,b,15
TEAEs, n (%)
D-VRd
(n=120)
VRd
(n=114)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Hematologic TEAEs
   Neutropeniac
80 (66.7)
71 (59.2)
61 (53.5)
49 (43.0)
   Thrombocytopenia
66 (55.0)
46 (38.3)
44 (38.6)
22 (19.3)
   Anemia
33 (27.5)
8 (6.7)
29 (25.4)
7 (6.1)
Nonhematologic TEAEs
   Diarrhea
71 (59.2)
17 (14.2)
66 (57.9)
12 (10.5)
   Peripheral sensory neuropathy
69 (57.5)
7 (5.8)
55 (48.2)
7 (6.1)
   Constipation
58 (48.3)
3 (2.5)
47 (41.2)
1 (0.9)
   Pyrexia
45 (37.5)
3 (2.5)
37 (32.5)
2 (1.8)
   Fatigue
44 (36.7)
6 (5.0)
39 (34.2)
7 (6.1)
   Upper respiratory tract infection
43 (35.8)
1 (0.8)
40 (35.1)
2 (1.8)
   Edema peripheral
43 (35.8)
4 (3.3)
35 (30.7)
3 (2.6)
   Cough
43 (35.8)
1 (0.8)
22 (19.3)
0 (0.0)
   Back pain
39 (32.5)
1 (0.8)
22 (19.3)
0 (0.0)
   Nausea
38 (31.7)
2 (1.7)
26 (22.8)
1 (0.9)
   Rash
33 (27.5)
4 (3.3)
24 (21.1)
8 (7.0)
   Arthralgia
30 (25.0)
0 (0.0)
25 (21.9)
1 (0.9)
   Insomnia
30 (25.0)
4 (3.3)
21 (18.4)
3 (2.6)
   Asthenia
26 (21.7)
2 (1.7)
31 (27.2)
2 (1.8)
   COVID-19
26 (21.7)
1 (0.8)
17 (14.9)
0 (0.0)
   Muscle spasms
24 (20.0)
2 (1.7)
27 (23.7)
2 (1.8)
   Bronchitis
24 (20.0)
2 (1.7)
13 (11.4)
1 (0.9)
   Pneumonia
23 (19.2)
13 (10.8)
17 (14.9)
7 (6.1)
   Hypokalemia
23 (19.2)
5 (4.2)
26 (22.8)
7 (6.1)
Abbreviations: D-VRd, DARZALEX FASPRO/DARZALEX + bortezomib + lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; VRd, bortezomib + lenalidomide + dexamethasone.
aTEAEs of any grade that occurred in ≥20% of patients aged ≥65 years in either treatment group, or grade 3/4 TEAEs that occurred in ≥10% of patients aged ≥65 years in either treatment group.
bThe pooled safety population includes all patients who were randomized in GRIFFIN or PERSEUS and received ≥1 dose of study treatment.
cNeutropenia as a grouped term that included the preferred terms neutropenia and febrile neutropenia.

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 23 July 2025.

 

References

Show
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2 Voorhees PM, Kaufman J, Laubach J, et al. Daratumumab + lenalidomide, bortezomib & dexamethasone improves depth of response in transplant-eligible newly diagnosed multiple myeloma: GRIFFIN. Oral Presentation presented at: The 17th International Myeloma Workshop (IMW); September 12-15, 2019; Boston, MA.  
3 Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945.  
4 Voorhees PM, Rodriguez C, Reeves B, et al. Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN. Blood Adv. 2021;5(4):1092-1096.  
5 Laubach J, Kaufman JL, Sborov DW, et al. Daratumumab (DARA) plus lenalidomide, bortezomib, and dexamethasone (RVd) in patients (pts) with transplant-eligible newly diagnosed multiple myeloma (NDMM): updated analysis of GRIFFIN after 24 months of maintenance. Oral Presentation presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual Meeting.  
6 Voorhees PM, Sborov DW, Laubach J, et al. Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial. Lancet Haematol. 2023;10(10):e825-e837.  
7 Rodriguez C, Kaufman J, Laubach J, et al. Daratumumab + lenalidomide, bortezomib, and dexamethasone in transplant-eligible newly diagnosed multiple myeloma: a post hoc analysis of sustained minimal residual disease negativity from GRIFFIN. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL/Virtual Meeting.  
8 Nooka AK, Kaufman JL, Rodriguez C, et al. Post hoc analysis of daratumumab plus lenalidomide, bortezomib, and dexamethasone in black patients from final data of the GRIFFIN study. Br J Haematol. 2024; 204(6):2227-2232.  
9 Chari A, Kaufman JL, Laubach J, et al. Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN. Blood Cancer J. 2024;14(1):107.  
10 Callander NS, Silbermann R, Kaufman JL, et al. Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk. Blood Cancer J. 2024;14(1):69.  
11 Sborov D, Baljevic M, Reeves B, et al. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: analysis of vascular thrombotic events in the GRIFFIN study. Clin Lymphoma Myeloma Leuk. 2022;199(3):355-365.  
12 Silbermann R, Laubach J, Kaufman JL, et al. Reduction in disease symptoms/impacts after daratumumab, lenalidomide, bortezomib, and dexamethasone treatment for transplant-eligible patients with newly diagnosed multiple myeloma (GRIFFIN study). Poster presented at: 20th International Myeloma Society (IMS) Annual Meeting and Exposition; September 27-30, 2023; Athens, Greece.  
13 Silbermann R, Laubach J, Kaufman JL, et al. Health‐related quality of life in transplant‐eligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, bortezomib, and dexamethasone: Patient‐reported outcomes from GRIFFIN. Am J Hematol. 2024;99(7):1257-1268.  
14 Chhabra S, Callander N, Watts N, et al. Stem cell mobilization yields with daratumumab- and lenalidomide-containing quadruplet induction therapy in newly diagnosed multiple myeloma: findings from the MASTER and GRIFFIN trials. Transplant Cell Ther. 2023;29(3):174.e1-174.e10.  
15 Rodriguez-Otero P, Voorhees PM, Boccadoro M, et al. Daratumumab for newly diagnosed multiple myeloma: pooled analysis of patients aged ≥65 years from GRIFFIN and PERSEUS. [Published online ahead of print April 11, 2025]. Clin Lymphoma Myeloma Leuk. 2025. doi:10.1016/j.clml.2025.04.007.  
16 Voorhees P, Kaufman J, Laubach J, et al. Depth of response to daratumumab (DARA), lenalidomide, bortezomib, and dexamethasone (RVd) improves over time in patients (pts) with transplant-eligible newly diagnosed multiple myeloma (NDMM): GRIFFIN study update. Oral Presentation presented at: 61st American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL.  
17 Kaufman J, Laubach J, Sborov D, et al. Daratumumab (DARA) plus lenalidomide, bortezomib, and dexamethasone (RVd) in patients with transplant-eligible newly diagnosed multiple myeloma (NDMM): updated analysis of GRIFFIN after 12 months of maintenance therapy. Oral Presentation presented at: 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; San Diego, CA.  
18 Voorhees PM, Sborov DW, Laubach J, et al. Supplement to: Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial. Lancet Haematol. 2023;10(10):e825-e837.  
19 Nooka A, Kaufman J, Rodriguez C, et al. Daratumumab + lenalidomide/bortezomib/dexamethasone in African American/Black patients with transplant eligible newly diagnosed multiple myeloma: subgroup analysis of GRIFFIN. Poster presented at: 8th Annual Meeting of the Society of Hematologic Oncology; September 9-12, 2020; Virtual Meeting.  
20 Nooka AK, Kaufman JL, Rodriguez C, et al. Daratumumab plus lenalidomide/bortezomib/dexamethasone in Black patients with transplant-eligible newly diagnosed multiple myeloma in GRIFFIN. Blood Cancer J. 2022;12(4):63.  
21 Nooka A, Kaufman J, Rodriguez C, et al. Daratumumab (DARA) + lenalidomide/bortezomib/dexamethasone (RVd) in black patients with transplant-eligible newly diagnosed multiple myeloma (NDMM): an updated subgroup analysis of GRIFFIN. Poster presented at: 19th International Myeloma Society (IMS) Annual Meeting; August 25-27, 2022; Los Angeles, CA.  
22 Nooka AK, Kaufman JL, Rodriguez C, et al. Supplement to: Post hoc analysis of daratumumab plus lenalidomide, bortezomib, and dexamethasone in black patients from final data of the GRIFFIN study. Br J Haematol. 2024;00: 204(6):2227-2232.  
23 Chari A, Kaufman JL, Laubach J, et al. Supplement to: Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN. Blood Cancer J. 2024;14(1):107.  
24 Silbermann R, Laubach J, Laubach J, et al. Supplement to: Health‐related quality of life in transplant‐eligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, bortezomib, and dexamethasone: Patient‐reported outcomes from GRIFFIN. Am J Hematol. 2024;99(7):1257-1268.  
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