DARZALEX FASPRO®

(daratumumab and hyaluronidase-fihj)

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DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)

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Use of DARZALEX + DARZALEX FASPRO in Combination with Bortezomib, Lenalidomide, and Dexamethasone in Multiple Myeloma

Last Updated: 05/14/2025

Summary

DARZALEX for intravenous (IV) use 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: 2-part, phase 2 study evaluating the safety and efficacy of DARZALEX (D) when administered in combination with VRd in patients with newly diagnosed MM (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 DARZALEX in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) consolidation, 56.3% patients achieved stringent complete response (sCR), and 50% were minimal residual disease (MRD) negative (10^-5threshold). After maintenance, 93.8% patients achieved sCR, and 81.3% patients were MRD-negative (10^-5threshold). 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)³ presented the primary analysis of the randomized portion of this study (n=207). Voorhees et al (2023)⁵ 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%).
PERSEUS: phase 3 study evaluating the efficacy and safety of DARZALEX FASPRO in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) vs VRd induction and consolidation followed by maintenance with lenalidomide and DARZALEX FASPRO (D-R) in D-VRd group or lenalidomide (R) in VRd group in patients with NDMM eligible for ASCT.⁶
- Sonneveld et al (2023)⁶ reported efficacy and safety results from the PERSEUS study evaluating D-VRd vs VRd in patients with NDMM eligible for ASCT. At a median follow-up duration of 47.5 months (range, 0-54.4), 14.1% (50/355) of patients in the D-VRd arm vs 29.1% (103/354) of patients in the VRd arm experienced disease progression or death (hazard ratio [HR], 0.42; 95% CI, 0.30-0.59; P<0.0001), respectively. Overall ≥CR, 87.9% vs 70.1% (P<0.0001) and overall MRD-negativity 75.2% vs 47.5% (P<0.0001) were higher with D-VRd vs VRd. The most common grade 3/4 adverse events (AEs) in the D-VRd vs VRd arm were neutropenia (62.1% vs 51%), thrombocytopenia (29.1% vs 17.3%), diarrhea (10.5% vs 7.8%), pneumonia (10.5% vs 6.1%), and febrile neutropenia (9.4% vs 10.1%).
CEPHEUS: phase 3 study evaluating the efficacy and safety of DARZALEX FASPRO in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) or VRd in patients with NDMM who are transplant ineligible (TIE) or for whom transplant is not planned as initial therapy (transplant deferred). The trial has enrolled 395 patients in 13 countries.⁷^-⁹
- Usmani et al (2025)⁹ reported results from the phase 3 CEPHEUS study. At a median follow-up of 58.7 months (range, 0.1-64.7), the overall MRD-negativity (10^-5 sensitivity with ≥CR) rate was significantly higher with D-VRd vs VRd (60.9% vs 39.4%; OR, 2.37; 95% CI, 1.58-3.55; P<0.0001). Similarly, the sustained MRD-negativity (10^-5 sensitivity; ≥12 months) rate was significantly higher in the D-VRd vs VRd arm (48.7% vs 26.3%; OR, 2.63; 95% CI, 1.73-4; P<0.0001). The overall ≥CR rate was significantly higher with D-VRd vs VRd (81.2% vs 61.6%; OR, 2.73; 95% CI, 1.71-4.34; P<0.0001). Further, D-VRd significantly improved the PFS (HR, 0.57; 95% CI, 0.41-0.79; P=0.0005) with 43% reduction in the risk of progression or death vs VRd. The overall survival (OS) rate favored the D-VRd vs VRd arm (HR, 0.85; 95% CI, 0.58-1.24). Serious TEAEs occurred in 142 (72.1%) vs 131 (67.2%) of patients from the D-VRd vs VRd arm, respectively, with the most common serious TEAE being pneumonia (D-VRd, 13.7%; VRd, 12.8%). The overall safety data were consistent with the established safety profile of each individual drug.
- Zweegman et al (2024)¹⁰ presented an expanded analysis of MRD outcomes from the CEPHEUS study in patients with NDMM who were ineligible for a stem cell transplant (SCT) or transplant deferred. The addition of DARZALEX FASPRO to VRd improved cumulative MRD-negativity rates (both 10^-5 and 10^-6 sensitivities) vs VRd alone at all prespecified timepoints. At 54 months, among patients who achieved both MRD-negativity (10^-6 sensitivity) and ≥CR with D-VRd, >85% were alive and progression free. Analyses of MRD-negativity (with ≥CR) rates in D-VRd vs VRd were generally consistent across prespecified subgroups.
PLEIADES: phase 2 study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with 4 standard-of-care treatment regimens in patients with MM. Specifically with transplant-eligible NDMM DARZALEX FASPRO + VRd (D-VRd) for patients with transplant-eligible NDMM (n=67).¹¹^-¹⁴ Results specifically to the D-VRd cohort are summarized.
Other relevant literature regarding the use of DARZALEX and DARZALEX FASPRO in combination with VRd in patients with MM has been identified in addition to the data summarized above.¹⁵^-²⁶

PRODUCT LABELING

DARZALEX (daratumumab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf.
DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.

CLINICAL STUDIES

DARZALEX Phase 2 Study

GRIFFIN (MMY2004; NCT02874742) is an ongoing, 2-part, open-label, multicenter, phase 2, randomized, active-controlled United States (US) study evaluating the safety and efficacy of DARZALEX in combination with VRd in patients with NDMM eligible for HDT and ASCT.¹^-³

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) 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

	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)
Female	8 (50)
Race, n (%)
White	11 (68.8)
Black or African American	4 (25)
Asian	1 (6.3)
ECOG performance status^a, n (%)
0	3 (18.8)
1	10 (62.5)
2	3 (18.8)
ISS disease stage^b, n (%)
I	12 (75)
II	2 (12.5)
III	2 (12.5)
Cytogenetic risk profile^c, n (%)
Standard	12 (75)
High risk	4 (25)
Median (range) time since diagnosis of multiple myeloma, months	1.6 (0-5)
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System. ^aECOG performance status 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

	D-VRd (n=16)
CD34⁺ yield, median (range) (x 10⁶ cells/kg)	8.05 (3.5-17.6)
CD34⁺ cells transplanted, median (range) (x 10⁶ cells/kg)	4.72 (2.2-6)
Patients receiving plerixafor for mobilization, n (%)	9 (56.3)
Patients receiving cyclophosphamide, n (%)	0 (0)
Days to neutrophil (0.5 x 10⁹/L) engraftment^a, median (maximum)	14
Days to platelet (20 x 10⁹/L) engraftment^b, median (maximum)	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, three of 16 patients developed 4 dose-limiting toxicities (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 infusion-related reactions (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 (68.6%) patients experienced a serious AE. For the incidences of grade 3/4 TEAEs, see Table: Most Common Grade 3/4 TEAEs.

Most Common Grade 3/4 TEAEs⁴

Patients, n (%)	D-VRd (n=16)
Patients, n (%)	Grade 3/4^a
Total	15 (93.8)
Most commonly occurring
Neutropenia	7 (43.8)
Pneumonia	5 (31.3)
Lymphopenia	5 (31.3)
Thrombocytopenia	4 (25)
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), disease progression occurred in 3 patients.
Median time to first response was 0.77 months (range, 0.1-2.1), and median duration of response 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-month PFS and OS rate 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 was sustained for ≥12 months in 8 (50%) 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 Cohort^a,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; 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^,²⁷ presented the primary analysis and updated analysis of the randomized portion of this study. Kaufman et al (2020)²⁸ presented a 1-year update of safety and efficacy results in December 2020. Laubach et al (2021)²⁹ presented updated efficacy and safety results after 2 years of maintenance therapy in the GRIFFIN Study. Voorhees et al (2023)⁵ 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 demographics 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 status^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 creatinine clearance, 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: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; ITT, intention-to-treat; MM, multiple myeloma; VRd, bortezomib + lenalidomide + dexamethasone. ^aECOG performance status 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

Primary endpoint met with D-VRd improving the sCR rate by end of consolidation (D-VRd vs VRd: 42.4% vs 32%; 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 group vs the VRd group (99% 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 intention-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 in Table: Post-Consolidation MRD-Negativity.
Median stem cell yield (D-VRd vs VRd): 8.2 vs 9.4 x 10⁶ cells.

Post-Consolidation MRD-Negativity³

MRD-Negative Status (10^-5), n (%); ITT^a	D-VRd (n=104)	VRd (n=103)	Odds Ratio (95% CI)^b	P-value^c
MRD-negative regardless of response	53/104 (51)	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)	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, intention-to-treat; MRD, minimal residual disease; NGS, next-generation sequencing; 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 odds ratio 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 odds ratio .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.
MRD-negativity rates in the D-VRd and VRd arms, respectively (10^-5 sensitivity threshold):
- D-VRd (n=104) and VRd (n=103) (ITT): MRD-negative: 51% vs 20.4% (P<0.0001); MRD-negative & ≥CR: 47.1% vs 18.4% (P<0.0001)
  - ≥CR: D-VRd (n=79) and VRd (n=59): MRD-negative: 62% vs 32.2% (P=0.0006)
  - MRD evaluable: D-VRd (n=77) and VRd (n=65): MRD-negative: 68.8% vs 32.3% (P<0.0001)
In the ITT population, median PFS and OS were not reached 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% 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 Transplantation²⁷

	D-VRd	VRd
Median (range) stem cell yield^a,b, x 10⁶ CD34⁺ cells/kg	8.2 (3-33)	9.4 (4-29)
Median stem cells transplanted^c, x 10⁶ CD34⁺ cells/kg	4.2	4.8
Patients receiving plerixafor for mobilization^d, n(%)	66 (70)	45 (56)
Patients receiving cyclophosphamide^d, n (%)	5 (5)	4 (5)
Median (max) days to neutrophil engraftment (0.5 x 10⁹/L)	12 (31)	12 (23)
Median (max) days to platelet engraftment (20 x 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 group had a stem cell yield <3 x 10⁶ cells/kg; no patients in either group had a stem cell yield <2 x 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. See Table: Most Common TEAEs.
- Pneumonia was reported in 13% of patients in the D-VRd arm and 15% of patients in the VRd arm. See Table: Most Common TEAEs.

Most Common TEAEs^a,³^,²⁷

Event, n (%)	D-VRd (n=99)		VRd (n=102)
Event, n (%)	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)
Non-hematologic
Fatigue	68 (68.7)	6 (6.1)	62 (60.8)	6 (5.9)
Upper respiratory tract infection	62 (62.6)	1 (1)	45 (44.1)	2 (2)
Peripheral neuropathy^b	59 (59.6)	7 (7.1)	74 (72.5)	8 (7.8)
Diarrhea	59 (59.6)	7 (7.1)	51 (50)	4 (3.9)
Constipation	51 (51.5)	2 (2)	40 (39.2)	1 (1)
Cough	50 (50.5)	0 (0)	27 (26.5)	0 (0)
Nausea	49 (49.5)	2 (2)	50 (49)	1 (1)
Pyrexia	45 (45.5)	2 (2)	28 (27.5)	3 (2.9)
Insomnia	42 (42.4)	2 (2)	31 (30.4)	1 (1)
Back pain	36 (36.4)	1 (1)	34 (33.3)	4 (3.9)
Edema peripheral	34 (34.3)	2 (2)	35 (34.3)	3 (2.9)
Arthralgia	33 (33.3)	0 (0)	33 (32.4)	2 (2)
Infusion-related reactions	42 (42.4)	6 (6)^c	-	-
Abbreviations: D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; VRd, bortezomib + lenalidomide + dexamethasone. ^aAny grade TEAEs are listed that occurred in ≥30% of patients in either group. 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 infusion-related reactions were reported.

Final Efficacy and Safety Analysis of Maintenance Therapy

Voorhees et al (2023)⁵ 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 [IQR, 3-5]).

Patient Disposition⁵

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.⁵^,³⁰

Summary of Response Over Time⁵

Timepoint, %	D-VRd						VRd
Timepoint, %	sCR	CR	≥CR	VGPR	PR	SD/PD/ NE	sCR	CR	≥CR	VGPR	PR	SD/PD/ NE
End of induction^a	12	7	19	53	26	2	7	6	13	43	35	8
End of post-ASCT consolidation^a	42	9	52	39	8	1	32	10	42	31	19	8
Final analysis^b	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 bettwe; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; IQR, interquartile range; 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).

The response duration among patients in the D-VRd vs VRd arm is presented in Table: Response Duration Among Patients in the D-VRd vs VRd Arm.

Response Duration Among Patients in the D-VRd vs VRd Arm⁵

Parameter	D-VRd	VRd
Median duration to first response (ORR), months (95% CI)	0.8 (0.8-0.8)	0.8 (0.8-1)
Median duration to sCR, months (95% CI)	10.2 (8.8-13)	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 (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.

Among patients who achieved ≥partial response (PR), 9% (n/N=9/99) in the D-VRd arm and 18% (n/N=16/90) in the VRd arm subsequently had PD (See Table: Final Analysis of Best Response and MRD-Negativity Rates at the End of Maintenance).

Final Analysis of Best Response and MRD-Negativity Rates at the End of Maintenance⁵^,³⁰

Parameter	D-VRd	VRd	P value
Response^a, n	100	98	-
ORR, n (%)	99 (99)	90 (92)	0.016^b
≥CR	83 (83)	59 (60)	0.0005^b
CR	16 (16)	12 (12)	-
sCR	67 (67)	47 (48)	0.0079^b
≥VGPR	96 (96)	76 (78)	0.0002^b
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^-5sensitivity, n (%)	67 (64)	31 (30)	<0.0001^c
OR (95% CI)	4.23 (2.35-7.62)
10^-6 sensitivity, n (%)	37 (36)	16 (16)	0.0013^c
OR (95% CI)	2.95 (1.52-5.75)
In patients achieving ≥CR, n	83	59	-
10^-5 sensitivity, n (%)	64 (77)	28 (47)	0.0004^c
10^-6 sensitivity, n (%)	35 (42)	14 (24)	0.031^c
Durable MRD-negativity
Lasting ≥12 months, n	104	103	-
10^-5 sensitivity, n (%)	46 (44)	14 (14)	<0.0001^c
OR (95% CI)	5 (2.50-9.99)
10^-6 sensitivity, n (%)	10 (10)	4 (4)	0.16^c
OR (95% CI)	2.48 (0.76-8.07)
Abbreviations: CI, confidence interval; ≥CR, complete response or better; CR, complete response; CrCl, creatinine clearance; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ISS, International Staging System; ITT, intention-to-treat; MM, multiple myeloma; MRD, minimal residual disease; 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 or better; 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,⁵^,³⁰

Timepoint, %	D-VRd		VRd
Timepoint, %	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; CR, complete response; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ITT, intention-to-treat; MRD, minimal residual disease; NGS, next-generation sequencing; sCR, stringent complete response; 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 not reached (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)⁵^,³⁰

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); 0.84^a
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 of 89 (4%) evaluable patients in the D-VRd arm and 3 of 71 (4%) 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 [39%] IRRs reported at the initial infusion, 2 [2%] IRRs at the second infusion, and 14 [14%] IRRs at the subsequent infusions.³⁰

Most Common TEAEs in the Safety Population^a,⁵^,³⁰

TEAEs, n (%)	D-VRd (n=99)			VRd (n=102)
TEAEs, n (%)	Grade 1/2	Grade 3	Grade 4	Grade 1/2	Grade 3	Grade 4
Hematologic
Anemia	28 (28)	9 (9)	0 (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)
Non-hematologic
Hypokalemia	24 (24)	3 (3)	1 (1)	24 (24)	3 (3)	0 (0)
Hypocalcemia	17 (17)	0 (0)	0 (0)	12 (12)	2 (2)	1 (1)
Pneumonia^b	11 (11)	11 (11)	1 (1)	4 (4)	14 (14)	0 (0)
Hyperkalemia	6 (6)	1 (1)	0 (0)	1 (1)	0 (0)	1 (1)
Cellulitis	6 (6)	0 (0)	1 (1)	3 (3)	1 (1)	0 (0)
Hypophosphatemia	5 (5)	9 (9)	1 (1)	6 (6)	11 (11)	0 (0)
Hyperuricemia	4 (4)	0 (0)	0 (0)	6 (6)	0 (0)	1 (1)
Acute kidney injury	2 (2)	2 (2)	2 (2)	4 (4)	3 (3)	0 (0)
Atrial fibrillation	1 (1)	0 (0)	1 (1)	3 (3)	0 (0)	0 (0)
Increased blood creatine phosphokinase	1 (1)	0 (0)	0 (0)	0 (0)	0 (0)	1 (1)
Atrial tachycardia	1 (1)	0 (0)	0 (0)	0 (0)	0 (0)	1 (1)
Sepsis	0 (0)	1 (1)	2 (2)	0 (0)	1 (1)	0 (0)
Drug reaction with eosinophilia and systemic symptoms	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (1)
Septic shock	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (1)
Cerebrovascular accident	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (1)
Systemic inflammatory response syndrome	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	1 (1)
Death	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
IRRs^c	49 (49)	7 (7)	0 (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.

DARZALEX FASPRO in Combination With Bortezomib, Lenalidomide, and Dexamethasone

PERSEUS (MMY3014; NCT03710603) is an ongoing, open-label, multicenter, phase 3 study evaluating the efficacy and safety of D-VRd vs VRd induction and consolidation followed by maintenance with D-R in D-VRd group or lenalidomide in VRd arm in patients with NDMM eligible for ASCT. Sonneveld et al (2023)⁶ reported efficacy and safety results from the PERSEUS study evaluating D-VRd vs VRd in patients with NDMM eligible for ASCT.

Results

Patient Characteristics

A total of 709 patients were randomized into the D-VRd (n=355) and VRd (n=354) arms.
Demographics and baseline clinical characteristics of the ITT population are presented in Table: Demographics and Baseline Clinical Characteristics of the ITT Population.
A total of 698 patients (D-VRd, n=351; VRd, n=347) received ≥1 dose of treatment.
As of the clinical data cutoff date of August 1, 2023, 322 (91.7%) vs 300 (86.5%) patients in the D-VRd vs VRd arm, who started the induction phase continued into the maintenance phase, respectively.
- A total of 207/322 patients in the D-VRd arm who were receiving maintenance treatment discontinued DARZALEX FASPRO per protocol after receiving ≥24 months of maintenance treatment and achieving ≥CR and sustained MRD-negativity for ≥12 months.
A total of 315 (89.7%) vs 302 (87%) patients in the D-VRd vs VRd arm received ASCT, respectively.
The median duration of treatment and median relative dose intensities are presented in Table: Duration of Treatment and Relative Dose Intensities During Induction/Consolidation/Maintenance Treatment in the Safety Population.
The median duration of follow-up was 47.5 months (range, 0-54.4).

Demographics and Baseline Clinical Characteristics of the ITT Population^a,⁶

	D-VRd (n=355)	VRd (n=354)
Median age (range), years	61 (32-70)	59 (31-70)
Male, n (%)	211 (59.4)	205 (57.9)
Race, n (%)
Asian	4 (1.1)	6 (1.7)
Black or African American	5 (1.4)	4 (1.1)
White	330 (93)	323 (91.2)
Other	4 (1.1)	3 (0.8)
Missing data	12 (3.4)	18 (5.1)
ECOG PS^b, n (%)
0	221 (62.3)	230 (65)
1	114 (32.1)	108 (30.5)
2	19 (5.4)	16 (4.5)
3	1 (0.3)	0 (0)
Type of measurable disease, n (%)
IgG	204 (57.5)	185 (52.3)
IgA	65 (18.3)	85 (24)
Other^c	13 (3.7)	11 (3.1)
Detected in urine only	43 (12.1)	46 (13)
Detected in serum free light chains only	29 (8.2)	27 (7.6)
Not evaluable	1 (0.3)	0 (0)
ISS disease stage^d, n	355	353
I, n (%)	186 (52.4)	178 (50.4)
II, n (%)	114 (32.1)	125 (35.4)
III, n (%)	55 (15.5)	50 (14.2)
Cytogenetic risk profile^e, n (%)
Standard risk	264 (74.4)	266 (75.1)
High risk	76 (21.4)	78 (22)
Indeterminate	15 (4.2)	10 (2.8)
Median time since diagnosis of multiple myeloma (range), months	1.2 (0-46.5)	1.1 (0.1-184.6)
Abbreviations: D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; Ig, immunoglobulin; ISS, International Staging System; ITT, intention-to-treat; VRd, bortezomib + lenalidomide + dexamethasone. ^aThe ITT population was defined as all patients who underwent randomization. Informal testing showed no significant differences between the 2 treatment groups in the characteristics evaluated at baseline. ^bECOG PS is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability. One patient had an ECOG PS score of 0 at the time of randomization that worsened to an ECOG PS score of 3 at baseline. ^cIncludes IgD, IgM, IgE, and biclonal. ^dThe ISS disease stage is based on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease. ^eCytogenetic risk was assessed by fluorescence in situ hybridization. High risk was defined as the presence of del(17p), t(4;14), and/or t(14;16).

Duration of Treatment and Relative Dose Intensities During Induction/Consolidation/Maintenance Treatment in the Safety Population^a,b,³¹

Median duration of treatment (range), months	D-VRd (n=351)				VRd (n=347)
Median duration of treatment (range), months	45.7 (0.5-54.3)				42.2 (0.1-53.9)
Median relative dose intensity (range), %	Induction		Consolidation	Maintenance	Induction	Consolidation	Maintenance
Bortezomib	(n=351) 98 (25.3-104.8)		(n=243) 97.8 (12.3-114.2)	NA	(n=347) 97.8 (40.2-110.4)	(n=236) 98.2 (9.5-106)	NA
Lenalidomide	(n=351) 100 (28.6-122.2)		(n=271) 100 (29.5-116.7)	(n=316) 85.2 (8.5-152.8)	(n=347) 100 (36.7-105.6)	(n=260) 100 (23.3-100)	(n=300) 97.1 (39.7-150.4)
Dexamethasone	(n=351) 100 (20.8-183.3)		(n=263) 100 (1.6-100)	NA	(n=347) 100 (35.9-121.9)	(n=250) 100 (10-125)	NA
	Induction Cycles 1-2 (n=351)	Induction Cycles 3-4 (n=343)	Consolidation (n=274)	Maintenance (n=322)
DARZALEX FASPRO	100 (50-100.4)	100 (25-100)	100 (50-100)	100 (67.6-100)	NA
Abbreviations: D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; NA, not available; VRd, bortezomib + lenalidomide + dexamethasone. ^aDose intensity was defined as the ratio of the total administered dose to the total planned dose. ^bThe safety population included all patients who received ≥1 dose of the study treatment.

Efficacy

A total of 50 (14.1%) vs 103 (29.1%) patients experienced disease progression or deaths in the D-VRd vs VRd arm of the ITT population (HR, 0.42; 95% CI, 0.30-0.59; P<0.0001), respectively, crossing the prespecified stopping boundary for superiority at the first interim analysis (P=0.0126).
The estimated 48-month PFS rate for the D-VRd vs VRd arm was 84.3% (95% CI, 79.5-88.1) vs 67.7% (95% CI, 62.2-72.6), respectively.
A summary of response rates and MRD status in the ITT population is presented in Table: Summary of Response Rates and MRD Status in the ITT Population.
Analyses of overall ≥CR rates and overall MRD-negativity rates (at 10^-5) in prespecified subgroups appeared to favor D-VRd over VRd across clinically relevant subgroups.
Information on PFS in prespecified subgroup analysis is summarized in Table: PFS in Prespecified Subgroups.

Summary of Response Rates and MRD Status in the ITT Population^a,⁶

Parameter	D-VRd (n=355)	VRd (n=354)	P Value^b
Overall response
n	343	332	-
% (95% CI)	96.6 (94.2-98.2)	93.8 (90.7-96.1)	-
Response, n (%)
≥CR	312 (87.9)	248 (70.1)	<0.0001
sCR^c	246 (69.3)	158 (44.6)	-
CR	66 (18.6)	90 (25.4)	-
≥VGPR	338 (95.2)	316 (89.3)	-
VGPR	26 (7.3)	68 (19.2)	-
PR	5 (1.4)	16 (4.5)	-
SD	4 (1.1)	9 (2.5)	-
PD	2 (0.6)	1 (0.3)	-
Response could not be evaluated	6 (1.7)	12 (3.4)	-
MRD-negativity^d, n (%)
10^-5 sensitivity	267 (75.2)	168 (47.5)	<0.0001
10^-6 sensitivity	231 (65.1)	114 (32.2)	-
Sustained MRD-negativity (10^-5) for ≥12 months, n (%)	230 (64.8)	105 (29.7)	-
Abbreviations: CI, confidence interval; CR, complete response; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; FLC, free light chain; IMWG, International Myeloma Working Group; ITT, intention-to-treat; MRD, minimal residual disease; NGS, next-generation sequencing; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone. ^aResponse rates and MRD-negativity rates at any time during the study. The responses were assessed based on the IMWG response criteria. ^bP values were calculated with the use of the stratified Cochran-Mantel-Haenszel chi-squared test. ^cCriteria for an sCR included the criteria for a CR plus a normal serum FLC ratio and the absence of clonal plasma cells in the bone marrow, as assessed by immunohistochemistry, immunofluorescence, or 2- to 4-color flow cytometry. ^dThe MRD-negativity rate was defined as the proportion of patients who achieved both MRD-negativity and ≥CR. Sustained MRD-negativity for 12 months was defined as 2 consecutive MRD-negative results 12 months apart, without any MRD-positive results in between. The MRD status was assessed using bone marrow samples and evaluated using an NGS assay (clonoSEQ assay, version 2; Adaptive Biotechnologies) in accordance with the IMWG guidelines for assessing MRD.

PFS in Prespecified Subgroups⁶

Subgroups	PFS
	D-VRd	VRd	D-VRd	VRd	HR (95% CI)
	No. of Progression Events or Deaths/Total no.		Median PFS, months		HR (95% CI)
Sex
Male	36/211	61/205	NE	NE	0.51 (0.34-0.77)
Female	14/144	42/149	NE	NE	0.29 (0.16-0.53)
Age
<65 years	30/261	84/267	NE	NE	0.30 (0.20-0.46)
≥65 years	20/94	19/87	NE	NE	0.97 (0.52-1.81)
Race
White	47/330	95/323	NE	NE	0.42 (0.30-0.60)
Other	3/25	8/31	NE	NE	0.40 (0.11-1.50)
ISS staging
I	18/186	35/178	NE	NE	0.46 (0.26-0.81)
II	19/114	43/125	NE	NE	0.37 (0.22-0.64)
III	13/55	25/50	NE	41.9	0.42 (0.22-0.83)
Type of MM
IgG	28/204	58/185	NE	NE	0.36 (0.23-0.57)
Non-IgG	13/78	31/96	NE	NE	0.46 (0.24-0.88)
Cytogenetic risk
Standard risk	25/264	62/266	NE	NE	0.35 (0.22-0.56)
High risk	24/76	38/78	NE	44.1	0.59 (0.36-0.99)
Intermediate risk	1/15	3/10	NE	NE	0.16 (0.02-1.56)
ECOG PS
0	28/221	60/230	NE	NE	0.42 (0.27-0.66)
≥1	22/134	43/124	NE	NE	0.41 (0.25-0.69)
Abbreviations: CI, confidence interval; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; Ig, immunoglobulin; ISS, International Staging System; MM, multiple myeloma; NE, not estimated; PFS, progression-free survival; VRd, bortezomib + lenalidomide + dexamethasone.

Safety

The most common grade 3/4 AEs recorded in the D-VRd vs VRd arm were neutropenia (62.1% vs 51%), thrombocytopenia (29.1% vs 17.3%), diarrhea (10.5% vs 7.8%), pneumonia (10.5% vs 6.1%), and febrile neutropenia (9.4% vs 10.1%). See Table: Most Common AEs During Treatment in the Safety Population.
Grade 3/4 peripheral neuropathy occurred in 6% vs 4.9% of patients in the D-VRd vs VRd arm, respectively.
Serious AEs (SAEs) in the safety population are summarized in Table: SAEs in the Safety Population.
A second primary malignancy was observed in 37 patients (10.5%) in the D-VRd arm and 25 patients (7.2%) in the VRd arm.
The number of deaths recorded due to COVID-19 in the D-VRd vs VRd arm was 4 (1.1%) vs 1 (0.3%) patients, respectively.
A total of 25.9% vs 54.2% of patients in the D-VRd vs VRd arm discontinued treatment, respectively.
- The most common reasons for treatment discontinuation over all phases of the study were AEs (D-VRd, 9.1%; VRd, 22.5%) and PD (D-VRd, 8.3%; VRd, 20.7%).
A total of 34 vs 44 patients died in the D-VRd vs VRd arm, respectively.
- A total of 7 patients died due to COVID-19 (D-VRd, n=4; VRd, n=3).

Most Common AEs During Treatment in the Safety Population^a,⁶

Event, n (%)	D-VRd (n=351)		VRd (n=347)
Event, n (%)	Any Grade	Grade 3/4	Any Grade	Grade 3/4
Any AE	349 (99.4)	321 (91.5)	344 (99.1)	297 (85.6)
Hematologic AEs
Neutropenia	243 (69.2)	218 (62.1)	204 (58.8)	177 (51)
Thrombocytopenia	170 (48.4)	102 (29.1)	119 (34.3)	60 (17.3)
Anemia	78 (22.2)	21 (6)	72 (20.7)	22 (6.3)
Febrile neutropenia	34 (9.7)	33 (9.4)	38 (11)	35 (10.1)
Nonhematologic AEs
Diarrhea	214 (61)	37 (10.5)	188 (54.2)	27 (7.8)
Peripheral sensory neuropathy	188 (53.6)	15 (4.3)	179 (51.6)	14 (4)
Constipation	119 (33.9)	8 (2.3)	118 (34)	6 (1.7)
Pyrexia	111 (31.6)	8 (2.3)	109 (31.4)	9 (2.6)
Insomnia	95 (27.1)	8 (2.3)	61 (17.6)	6 (1.7)
Asthenia	94 (26.8)	12 (3.4)	89 (25.6)	9 (2.6)
Cough	85 (24.2)	1 (0.3)	51 (14.7)	0 (0)
Fatigue	84 (23.9)	10 (2.8)	92 (26.5)	18 (5.2)
Rash	82 (23.4)	9 (2.6)	94 (27.1)	17 (4.9)
Back pain	80 (22.8)	2 (0.6)	66 (19)	1 (0.3)
Peripheral edema	72 (20.5)	4 (1.1)	74 (21.3)	1 (0.3)
Nausea	71 (20.2)	2 (0.6)	58 (16.7)	2 (0.6)
Infections	305 (86.9)	124 (35.3)	266 (76.7)	95 (27.4)
COVID-19	123 (35)	12 (3.4)	83 (23.9)	4 (1.2)
Upper respiratory tract infection	111 (31.6)	2 (0.6)	87 (25.1)	6 (1.7)
Pneumonia	64 (18.2)	37 (10.5)	38 (11)	21 (6.1)
Second primary malignancy	37 (10.5)	NA	25 (7.2)	NA
Any IRR	21 (6)	3 (0.9)	NA	NA
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; IRR, infusion-related reaction; NA, not applicable; VRd, bortezomib + lenalidomide + dexamethasone. ^aThe safety population included patients who received ≥1 dose of the study treatment. AEs of any grade that were reported in ≥20% of patients in either treatment group and grade 3/4 AEs that were reported in ≥10% of patients in either treatment group are listed.

SAEs in the Safety Population^a,³¹

n (%)	D-VRd (n=351)	VRd (n=347)
Total no. of patients with SAEs	200 (57)	171 (49.3)
SAEs occurring in ≥2% of patients in either treatment group
Infections	123 (35)	95 (27.4)
Pneumonia	40 (11.4)	21 (6.1)
COVID-19	13 (3.7)	6 (1.7)
COVID-19 pneumonia	11 (3.1)	5 (1.4)
Lower respiratory tract infection	9 (2.6)	3 (0.9)
Sepsis	7 (2)	9 (2.6)
Upper respiratory tract infection	7 (2)	8 (2.3)
Febrile neutropenia	16 (4.6)	16 (4.6)
Pyrexia	13 (3.7)	16 (4.6)
Pulmonary embolism	9 (2.6)	5 (1.4)
Atrial fibrillation	9 (2.6)	2 (0.6)
Diarrhea	7 (2)	9 (2.6)
Abbreviations: COVID-19, coronavirus disease 2019; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; SAE, serious adverse event; VRd, bortezomib + lenalidomide + dexamethasone. ^aThe safety population included patients who received ≥1 dose of the study treatment.

Median CD34+ cell yield in the D-VRd vs VRd arm was 5.5x10⁶/kg vs 7.4x10⁶/kg, respectively.
The proportion of patients proceeding to ASCT in the D-VRd vs VRd arm was 89.7% vs 87%, respectively.
The median time to complete hematopoietic reconstitution in the D-VRd vs VRd arm was 14 days each.

CEPHEUS (MMY3019; NCT03652064) is an ongoing, randomized, open-label, multicenter, phase 3 study evaluating the efficacy and safety of D-VRd vs VRd in patients with NDMM who are TIE or for whom transplant is not planned as initial therapy (transplant deferred).⁷^-⁹ Usmani et al (2025)⁹ reported results from the phase 3 CEPHEUS study.

Results

Patient Characteristics

A total of 395 patients were randomized into the D-VRd (n=197) and VRd (n=198) arms.⁹
The baseline demographics and clinical characteristics of the ITT population are presented in Table: Baseline Demographics and Clinical Characteristics of the ITT Population.
The median follow-up was 58.7 months (range, 0.1-64.7).⁹

Baseline Demographics and Clinical Characteristics of the ITT Population^a,⁹

Characteristic	D-VRd (n=197)	VRd (n=198)
Median age (range), years	70 (42-79)	70 (31-80)
<65 years, n (%)	36 (18.3)	35 (17.7)
65 to <70 years, n (%)	52 (26.4)	53 (26.8)
≥70 years, n (%)	109 (55.3)	110 (55.6)
Age or transplant eligibility, n (%)
<70 years and transplant ineligible	35 (17.8)	35 (17.7)
<70 years and transplant deferred	53 (26.9)	53 (26.8)
≥70 years	109 (55.3)	110 (55.6)
Male^b, n (%)	87 (44.2)	111 (56.1)
Race^b, n (%)
White	162 (82.2)	156 (78.8)
Black or African American	10 (5.1)	9 (4.5)
Asian	11 (5.6)	14 (7.1)
Native Hawaiian or other Pacific Islander	0 (0)	1 (0.5)
Other	1 (0.5)	2 (1)
Not reported	13 (6.6)	16 (8.1)
ECOG PS^c, n (%)
0	71 (36)	84 (42.4)
1	103 (52.3)	100 (50.5)
2	23 (11.7)	14 (7.1)
Frailty score^d, n (%)
0 (fit)	124 (62.9)	132 (66.7)
1 (intermediate fitness)	73 (37.1)	66 (33.3)
Type of measurable disease, n (%)
Detected in serum only	120 (60.9)	108 (54.5)
IgG	89 (45.2)	76 (38.4)
IgA	27 (13.7)	31 (15.7)
Other^e	4 (2)	1 (0.5)
Detected in serum and urine	41 (20.8)	45 (22.7)
Detected in urine only	20 (10.2)	24 (12.1)
Detected in serum FLCs only	16 (8.1)	21 (10.6)
ISS disease stage^f, n (%)
I	68 (34.5)	68 (34.3)
II	73 (37.1)	75 (37.9)
III	56 (28.4)	55 (27.8)
Cytogenetic risk profile^g, n (%)
Standard risk	149 (75.6)	149 (75.3)
High risk	25 (12.7)	27 (13.6)
Indeterminate^h	23 (11.7)	22 (11.1)
Median time since diagnosis of MM (range), months	1.2 (0.4-5.8)		1.3 (0.3-8)
Abbreviations: D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FLC, free light chain; Ig, immunoglobulin; ISS, International Staging System; ITT, intention-to-treat; MM, multiple myeloma; VRd, bortezomib + lenalidomide + dexamethasone. ^aThe ITT population was defined as all patients who underwent randomization. ^bSex and race were reported by the patient.^cECOG PS is scored on a scale of 0-5, with 0 indicating no symptoms and higher scores indicating increasing disability. ^dTotal additive frailty is scored on a scale of 0-5 based on age, comorbidities, and cognitive and physical conditions, with 0 indicating fit, 1 indicating intermediate fitness, and ≥2 indicating frail, per the Myeloma Geriatric Assessment score (http://www.myelomafrailtyscorecalculator.net/). ^eIncludes IgD, IgM, IgE, and biclonal.^fBased on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease. ^gAssessed by fluorescence in situ hybridization; high risk was defined as the presence of del(17p), t(4;14), and/or t(14;16). ^hIndeterminate includes patients with missing or unevaluable samples.

Efficacy

The duration of treatment and relative dose intensities are summarized in Table: Duration of Treatment and Relative Dose Intensities in the Safety Population.
As of the clinical cutoff date of May 7, 2024, 102 (51.8%) vs 67 (34.4%) patients from the D-VRd vs VRd arm, respectively, continued their treatment.⁹
A summary of the MRD status and response rates in the ITT population is presented in Table: Summary of MRD Status and Response Rates in the ITT Population.
- D-VRd vs VRd significantly increased the overall MRD-negativity rate (10^-5 sensitivity with ≥CR; 60.9% vs 39.4%) and ≥CR rate (81.2% vs 61.6%).⁹
- Patients in the D-VRd vs VRd arm showed a higher MRD-negativity rate at 10^-6 sensitivity (46.2% vs 27.3%) and a significantly higher sustained (≥12 months) MRD-negativity rate at 10^-5 sensitivity (48.7% vs 26.3%).⁹
- The treatment effect on the overall MRD-negativity rate remained consistent across the predefined subgroups and is summarized in Table: Prespecified Subgroup Analysis of Overall MRD-Negativity Rates.
At a median follow-up duration of 58.7 months, the median PFS was not reached in the D-VRd arm, while it was 52.6 months in the VRd arm.⁹
D-VRd significantly improved PFS with a 43% reduction in the risk of progression or death (HR, 0.57; 95% CI, 0.41-0.79; P=0.0005).⁹
At 54 months, the estimated PFS for D-VRd vs VRd was 68.1% (95% CI, 60.8-74.3) vs 49.5% (95% CI, 41.8-56.8).⁹
The treatment effect on PFS remained consistent across the predefined subgroups and is summarized in Table: PFS in Prespecified Subgroups.
Data for PFS on the subsequent line of therapy are still immature. However, HR favored D-VRd over VRd (HR, 0.78; 95% CI, 0.54-1.14) and further improved when censoring for death due to COVID-19 (HR, 0.60; 95% CI, 0.40-0.93).⁹
OS for ITT population favored the D-VRd vs VRd arm (HR, 0.85; 95% CI, 0.58-1.24) and further improved when censoring for death due to COVID-19 (HR, 0.69; 95% CI, 0.45-1.05).⁹
OS data were immature, and follow-up is ongoing.⁹
A lower proportion of patients who received subsequent therapy received an anti-CD38-based therapy in the D-VRd arm (3 of 22 patients [13.6%]) vs the VRd arm (39 of 65 patients [60%]).⁹
The EORTC QLQ-C30 global health status domain score improved over time in both arms, with no negative impact from the addition of DARZALEX FASPRO.⁹

Duration of Treatment and Relative Dose Intensities in the Safety Population^a,b,⁹

Parameter	D-VRd (n=197)	VRd (n=195)
Median duration of treatment (range), months	56.3 (0.1-64.6)	34.3 (0.5-63.8)
Median number of treatment cycles (range)	59 (1-71)	(1-70)
Median relative dose intensity (range)
Bortezomib	84.5 (12.7-104.3)	81.6 (22.4-102.1)
Lenalidomide	80.6 (2.5-248.2)	83.8 (25.7-246)
Dexamethasone	81.5 (19.6-177)	77.9 (23.4-173.4)
DARZALEX FASPRO
Cycles 1 and 2 (n=197)	100 (33.3-105.6)	-
Cycles 3 to 8 (n=191)	100 (33.3-101.1)	-
Cycle 9+ (n=175)	100 (10-100.4)	-
Abbreviations: D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; VRd, bortezomib + lenalidomide + dexamethasone. ^aDose intensity was defined as the ratio of total administered dose to total planned dose.^bThe safety population included all patients who received ≥1 dose of study treatment.

Summary of MRD Status and Response Rates in the ITT Population⁹

Parameter	D-VRd (n=197)	VRd (n=198)	OR (95% CI)	P Value
Overall MRD-negativity^a, %
10^-5 sensitivity	60.9	39.4	2.37 (1.58-3.55)	<0.0001
10^-6 sensitivity	46.2	27.3	2.24 (1.48-3.40)	0.0001
Sustained MRD-negativity (10^‒5) for ≥12 months, %	48.7	26.3	2.63 (1.73-4)	<0.0001
Response^b, n	191	184	-	-
ORR, % (95% CI)	97 (93.5-98.9)	92.9 (88.4-96.1)	-	0.0698
sCR, n (%)	128 (65)	88 (44.4)	-	<0.0001
CR, n (%)	32 (16.2)	34 (17.2)	-	-
VGPR, n (%)	23 (11.7)	50 (25.3)	-	-
PR, n (%)	8 (4.1)	12 (6.1)	-	-
≥CR, n (%)	160 (81.2)	122 (61.6)	2.73 (1.71-4.34)	<0.0001
≥VGPR, n (%)	183 (92.9)	172 (86.9)	-	0.0495
SD, n (%)	5 (2.5)	7 (3.5)	-	-
PD, n (%)	0 (0)	0 (0)	-	-
Response could not be evaluated, n (%)	1 (0.5)	7 (3.5)	-	-
Abbreviations: CI, confidence interval; CR, complete response; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; IMWG, International Myeloma Working Group; ITT, intention-to-treat; MRD, minimal residual disease; 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. ^aMRD-negativity rate was defined as the proportion of patients who achieved both MRD-negativity (10^-5 threshold) and ≥CR. ^bResponse rates at any time during the study. Response was assessed based on IMWG response criteria. P values were calculated using the stratified Cochran-Mantel-Haenszel chi-squared test.

Prespecified Subgroup Analysis of Overall MRD-Negativity Rates⁹

Subgroup	D-VRd	VRd	OR (95% CI)
Subgroup	Number of Patients With MRD-Negativity/ Total Number of Patients (%)		OR (95% CI)
Sex
Male	54/87 (62.1)	39/111 (35.1)	3.02 (1.69-5.41)
Female	66/110 (60)	39/87 (44.8)	1.85 (1.04-3.26)
Age
<70 years	59/88 (67)	36/88 (40.9)	2.94 (1.59-5.44)
≥70 years	61/109 (56)	42/110 (38.2)	2.06 (1.20-3.53)
Region
Europe	69/120 (57.5)	46/116 (39.7)	2.06 (1.23-3.46)
North America	21/37 (56.8)	13/31 (41.9)	1.82 (0.69-4.77)
Other	30/40 (75)	19/51 (37.3)	5.05 (2.03-12.60)
Weight
≤65 kg	40/58 (69)	22/63 (34.9)	4.14 (1.94-8.86)
>65-85 kg	58/101 (57.4)	31/88 (35.2)	2.48 (1.38-4.47)
>85 kg	22/38 (57.9)	25/47 (53.2)	1.21 (0.51-2.87)
ISS staging
I	45/68 (66.2)	30/68 (44.1)	2.48 (1.24-4.96)
II	47/73 (64.4)	29/75 (38.7)	2.87 (1.47-5.59)
III	28/56 (50)	19/55 (34.5)	1.89 (0.88-4.07)
Cytogenetic risk
High risk	12/25 (48)	15/27 (55.6)	0.74 (0.25-2.20)
Standard risk	95/149 (63.8)	57/149 (38.3)	2.84 (1.78-4.54)
Indeterminate	13/23 (56.5)	6/22 (27.3)	3.47 (0.99-12.09)
ECOG PS score
0	41/71 (57.7)	36/84 (42.9)	1.82 (0.96-3.45)
≥1	79/126 (62.7)	42/114 (36.8)	2.88 (1.71-4.87)
Abbreviations: CI, confidence interval; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; MRD, minimal residual disease; OR, odds ratio; VRd, bortezomib + lenalidomide + dexamethasone.

PFS in Prespecified Subgroups⁹

Subgroups	D-VRd	VRd	D-VRd	VRd	HR (95% CI)
Subgroups	Number of Disease Progression Events or Deaths/Total Number of Patients		Median PFS, months		HR (95% CI)
Sex
Male	24/87	53/111	NE	49.2	0.46 (0.29-0.75)
Female	39/110	38/87	NE	NE	0.73 (0.47-1.15)
Age
<70 years	30/88	38/88	NE	NE	0.72 (0.44-1.16)
≥70 years	33/109	53/110	NE	49.4	0.50 (0.33-0.78)
Region
Europe	37/120	54/116	NE	51.1	0.54 (0.36-0.82)
North America	10/37	13/31	NE	50.2	0.51 (0.22-1.17)
Other	16/40	24/51	NE	NE	0.87 (0.46-1.64)
Weight
≤65 kg	17/58	24/63	NE	NE	0.62 (0.34-1.16)
>65-85 kg	34/101	40/88	NE	51.1	0.65 (0.41-1.02)
>85 kg	12/38	27/47	NE	41.9	0.46 (0.23-0.91)
ISS staging
I	21/68	28/68	NE	60.6	0.66 (0.37-1.16)
II	18/73	37/75	NE	45.6	0.36 (0.21-0.64)
III	24/56	26/55	NE	49.2	0.84 (0.48-1.46)
Cytogenetic risk
High risk	13/25	17/27	39.8	31.7	0.88 (0.42-1.84)
Standard risk	43/149	60/149	NE	60.6	0.61 (0.41-0.91)
Indeterminate	7/22	14/22	NE	47.9	0.33 (0.13-0.82)
ECOG PS score
0	16/71	30/84	NE	NE	0.53 (0.29-0.97)
≥1	47/126	61/114	NE	43.8	0.59 (0.40-0.86)
Abbreviations: CI, confidence interval; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; ISS, International Staging System; NE, not estimated; PFS, progression-free survival; VRd, bortezomib + lenalidomide + dexamethasone.

Safety

A total of 95 vs 128 patients from the D-VRd vs VRd arm, respectively, discontinued treatment.⁹
- Reasons for treatment discontinuation in the D-VRd vs VRd arm, respectively, included:
  - Progressive disease: 27 (13.7%) vs 51 (26.2%) patients.
  - Adverse events (AEs): 16 vs 32 patients.
  - Deaths: 34 vs 24 patients.
    - COVID-19-related deaths: 12 (6.1%) vs 6 (3.1%) patients.
  - Refused further treatment: 15 vs 8 patients.
  - Physician decision: 3 vs 12 patients.
  - Received concurrent treatment for MM prior to disease progression: 0 vs 1 patient.
- Treatment discontinuation due to TEAEs was observed in 7.6% vs 15.9% of patients from the D-VRd vs VRd arm, respectively.
The safety data were consistent with the established safety profile of each individual drug.⁹ TEAEs in the safety population are summarized in Table: Most Common TEAEs in the Safety Population.
- Overall, deaths were reported in 51 vs 60 patients from the D-VRd vs VRd arm, respectively and are summarized in Table: Summary of Deaths in the ITT Population.
  - The COVID-19 pandemic impacted OS with 24 (21.6%) of all deaths in the study attributed to COVID-19 (D-VRd, n=15 vs VRd, n=9).
  - Overall, 21 COVID-19 deaths occurred during the peak of the pandemic in 2020 and 2021, with 3 additional deaths in 2022 (post-vaccine availability), and none in 2023 or 2024.
  - Regional variations were observed in pandemic impact. Brazil reported 54.2% of COVID-19 deaths (17.5% of the study population), while Poland had 16.7% of deaths (18.7% of the study population).
  - Two sensitivity analyses of OS adjusting for COVID-19 deaths showed a stronger treatment effect for D-VRd vs VRd (censoring COVID-19 deaths [HR, 0.69; 95% CI, 0.45-1.05] and considering COVID-19 deaths as a competing risk [HR for non-COVID mortality, 0.67; 95% CI, 0.44-1.03]).
- Grade 5 non-COVID-related TEAEs occurred in 10.7% vs 7.7% of patients from the D-VRd vs VRd arm, respectively.
- Serious TEAEs occurred in 142 (72.1%) vs 131 (67.2%) of patients from the D-VRd vs VRd arm, respectively, with the most common serious TEAE being pneumonia (D-VRd, 13.7%; VRd, 12.8%). A summary of the serious TEAEs is presented in Table: Serious TEAEs (≥2%) in the Safety Population.
- Most grade 5 TEAEs occurred after the discontinuation of bortezomib (cycle 8) in both arms (D-VRd, 13%; VRd, 9%). When adjusted for treatment exposure, the rate of grade 5 TEAEs was similar between the two arms (D-VRd, 0.39 per 100 patient-months; VRd, 0.31 per 100 patient-months).

Most Common TEAEs in the Safety Population^a,⁹

TEAE, n (%)	D-VRd (n=197)		VRd (n=195)
TEAE, n (%)	Any Grade	Grade 3/4	Any Grade	Grade 3/4
Hematologic
Neutropenia	110 (55.8)	87 (44.2)	76 (39)	58 (29.7)
Thrombocytopenia	92 (46.7)	56 (28.4)	66 (33.8)	39 (20)
Anemia	73 (37.1)	26 (13.2)	62 (31.8)	23 (11.8)
Lymphopenia	36 (18.3)	24 (12.2)	34 (17.4)	20 (10.3)
Nonhematologic
Diarrhea	112 (56.9)	24 (12.2)	115 (59)	18 (9.2)
Peripheral sensory neuropathy	110 (55.8)	16 (8.1)	119 (61)	16 (8.2)
Peripheral edema	83 (42.1)	4 (2)	76 (39)	1 (0.5)
Constipation	75 (38.1)	4 (2)	82 (42.1)	5 (2.6)
Insomnia	63 (32)	4 (2)	63 (32.3)	2 (1)
Fatigue	63 (32)	18 (9.1)	60 (30.8)	16 (8.2)
Hypokalemia	58 (29.4)	24 (12.2)	25 (12.8)	12 (6.2)
Cataract	55 (27.9)	17 (8.6)	51 (26.2)	17 (8.7)
Back pain	55 (27.9)	6 (3)	43 (22.1)	6 (3.1)
Cough	53 (26.9)	1 (0.5)	38 (19.5)	2 (1)
Asthenia	51 (25.9)	7 (3.6)	40 (20.5)	5 (2.6)
Rash	50 (25.4)	5 (2.5)	48 (24.6)	3 (1.5)
Nausea	49 (24.9)	0 (0)	48 (24.6)	4 (2.1)
Pyrexia	46 (23.4)	2 (1)	30 (15.4)	1 (0.5)
Arthralgia	45 (22.8)	3 (1.5)	39 (20)	0 (0)
Decreased appetite	42 (21.3)	2 (1)	39 (20)	5 (2.6)
Dizziness	41 (20.8)	1 (0.5)	41 (21)	2 (1)
Infections	181 (91.9)	79 (40.1)	167 (85.6)	62 (31.8)
Upper respiratory tract infection	78 (39.6)	1 (0.5)	64 (32.8)	1 (0.5)
COVID-19	75 (38.1)	22 (11.2)	48 (24.6)	9 (4.6)
Pneumonia	48 (24.4)	28 (14.2)	39 (20)	25 (12.8)
Urinary tract	41 (20.8)	7 (3.6)	29 (14.9)	5 (2.6)
Second primary malignancy^b	15 (7.6)	-	18 (9.2)	-
Any injection-related reaction	7 (3.6)	1 (0.5)^c	-	-
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; VRd, bortezomib + lenalidomide + dexamethasone. ^aThe safety population included patients who received ≥1 dose of study treatment. AEs of any grade that were reported in ≥20% of patients in either treatment arm and grade 3/4 AEs that were reported in ≥10% of patients in either treatment arm are listed. ^bOf all second primary malignancies, cutaneous malignancies were reported in 7 (3.6%) vs 7 (3.6%) patients from the D-VRd vs VRd arm, respectively.^cGrade 3.

Summary of Deaths in the ITT Population^a,⁹

Parameter, n	D-VRd (n=197)	VRd (n=195)
Overall deaths	51	60
PD	8	16
AE^b	37	25
COVID-19	7	5
COVID-19 pneumonia	5	1
Pneumonia	3	4
Death/sudden death	3	1
Cardiac arrest	2	1
General physical health deterioration	2	-
Drug induced liver injury	1	-
COVID-19, multiple organ dysfunction syndrome, and pulmonary embolism	1	-
Colitis	1	-
Sudden cardiac death	1	-
Respiratory failure	1	-
Acute kidney injury/failure	1	1
Dyspnea	1	-
Pulmonary embolism	1	-
Pulmonary fibrosis	-	1
Myocardial infarction	1	1
Acute myocardial infarction, cardiogenic shock	-	1
Multiple organ dysfunction syndrome	-	1
Lung neoplasm malignant	-	1
Completed suicide	-	1
Hypovolemic shock	-	1
Septic shock	1	1
Sepsis	-	2
Urinary tract infection	-	1
Cerebrovascular accident	1	-
Cardiopulmonary failure	1	-
Hepatic failure	-	1
Febrile neutropenia	1	-
Abdominal pain	1	-
Esophageal adenocarcinoma	1	-
Other^b	6	19
Unknown	3	10
COVID-19 or COVID-19 positive/infection	1	2
Acute hypoxic respiratory failure due to COVID-19	1	-
COVID-19 bronchopneumonia bilat.	-	1
Severe acute hepatitis	1	-
No more information available	-	1
Pneumocystosis infection	-	1
Ischemic bowel stroke	-	1
Acute kidney injury^c	-	1
Cholengiocellular carcinoma intrahepatic metastasis	-	1
Renal failure, possibility of PD	-	1
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; PD, progressive disease; VRd, bortezomib + lenalidomide + dexamethasone. ^aUntil the clinical cutoff. ^bSubcategory terms are listed as originally entered in the database by the investigator.^cPatient died following admission and was outside AE reporting window.

Serious TEAEs (≥2%) in the Safety Population^a,⁹

TEAE, n (%)	D-VRd (n=197)	VRd (n=195)
Serious TEAEs	142 (72.1)	131 (67.2)
Infections	78 (39.6)	69 (35.4)
Pneumonia	27 (13.7)	25 (12.8)
COVID-19	22 (11.2)	16 (8.2)
COVID-19 pneumonia	8 (4.1)	4 (2.1)
Sepsis	7 (3.6)	4 (2.1)
Urinary tract infection	7 (3.6)	4 (2.1)
Septic shock	6 (3 )	1 (0.5)
Gastroenteritis	4 (2)	4 (2.1)
Influenza	4 (2)	1 (0.5)
Pulmonary embolism	11 (5.6)	5 (2.6)
Diarrhea	10 (5.1)	6 (3.1)
Atrial fibrillation	7 (3.6)	7 (3.6)
Acute kidney injury	6 (3)	3 (1.5)
Asthenia	6 (3)	2 (1)
Anemia	6 (3)	2 (1)
Cataract	5 (2.5)	4 (2.1)
Pvrexia	5 (2.5)	3 (1.5)
Hypokalemia	5 (2.5)	3 (1.5)
Hyponatremia	5 (2.5)	1 (0.5)
Febrile neutropenia	4 (2)	4 (2.1)
Thrombocytopenia	4 (2)	2 (1)
Deep vein thrombosis	4 (2)	2 (1)
Syncope	3 (1.5)	6 (3.1)
Hypotension	3 (1.5)	4 (2.1)
Orthostatic hypotension	2 (1)	5 (2.6)
Dehydration	0 (0)	5 (2.6)
Abbreviations: COVID-19, coronavirus disease 2019; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; VRd, bortezomib + lenalidomide + dexamethasone. ^aThe safety population included patients who received ≥1 dose of study treatment.

Expanded Analysis of MRD Outcomes - Results From the CEPHEUS Study

Zweegman et al (2024)¹⁰ presented an expanded analysis of MRD outcomes from the CEPHEUS study in patients with NDMM who were ineligible for SCT or for whom transplant was deferred.

Results

Patient Characteristics

A total of 395 patients were randomized into the D-VRd (n=197) and VRd (n=198) arms.¹⁰

Efficacy

A summary of the cumulative and sustained MRD-negativity (≥CR) rates is presented in Table: Summary of Cumulative and Sustained MRD-Negativity (≥CR) Rates - CEPHEUS Expanded Analysis.
- D-VRd improved cumulative MRD-negativity rates (both 10^-5 and 10^-6sensitivities) vs VRd alone at all prespecified timepoints.¹⁰
- D-VRd almost doubled sustained MRD-negativity (≥) CR rates at 12, 24, and 36 months.¹⁰
- Among patients who achieved both MRD-negativity (10^-6sensitivity) and ≥CR with D-VRd, >85% were alive and progression free at 54 months.¹⁰
D-VRd vs VRd showed PFS benefit regardless of an MRD-negativity status (10^-6sensitivity).¹⁰
- The overall MRD-negativity rate (10^-6 sensitivity) for D-VRd vs VRd was 46.2% vs 27.3%, respectively and the overall MRD-positivity rate (10^-6 sensitivity) was 53.8% vs 72.7%, respectively.
- At 54 months, the estimated PFS by MRD-negativity status (10^-6 sensitivity) was 86.2% vs 79% and by MRD-positivity status was 51% vs 36.5% for D-VRd vs VRd, respectively.
Analyses of MRD-negativity (with ≥CR) rates in prespecified subgroups appeared to consistently favor D-VRd over VRd across these prespecified subgroups and are summarized in Table: MRD-Negativity (≥CR) Rates in Prespecified Subgroups.

Summary of Cumulative and Sustained MRD-Negativity (≥CR) Rates - CEPHEUS Expanded Analysis¹⁰

Parameter	D-VRd (n=197)	VRd (n=198)	OR (95% CI)	P Value
Cumulative MRD-negativity (10^-5 sensitivity; ≥CR), %
12 months	43.1	28.3	-	-
24 months	56.9	35.9	-	-
36 months	59.9	37.4	-	-
48 months	60.9	38.4	-	-
Cumulative MRD-negativity (10^-6 sensitivity; ≥CR), %
12 months	22.8	11.1	-	-
24 months	38.1	22.2	-	-
36 months	40.6	25.3	-	-
48 months	45.2	27.3	-	-
Sustained MRD-negativity (10^-5 sensitivity; ≥CR)^a, %
≥12 months^b	49.2	27.3	2.56 (NR)	<0.0001
≥24 months^c	42.1	22.7	2.47 (NR)	<0.0001
≥36 months^d	29.9	15.2	2.37 (NR)	0.0005
Sustained MRD-negativity (10^-6sensitivity; ≥CR)^a, %
≥12 months^b	34	16.2	NR	NR
≥24 months^c	27.9	13.6	NR	NR
≥36 months^d	18.8	8.6	NR	NR
Abbreviations: CI, confidence interval; CR, complete response; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; MRD, minimal residual disease; NR, not reported; OR, odds ratio; VRd, bortezomib + lenalidomide + dexamethasone. ^aAt any time during the study. ^bProportion of patients who achieved ≥CR and achieved an MRD-negative status at 2 bone marrow assessments that are 12 month apart with an allotted window of ±1 month, without an MRD-positive status in between. ^cAchieving an MRD-negative status at 2 bone marrow assessments that are 24 months apart with an allotted window of ±3 months, without an MRD-positive status in between. ^dAchieving an MRD-negative status at 2 bone marrow assessments that are 36 months apart with an allotted window of ±3 months, without an MRD-positive status in between.

MRD-Negativity (≥CR) Rates in Prespecified Subgroups¹⁰

Subgroups, n/N (%)	D-VRd	VRd	OR (95% CI)	D-VRd	VRd	OR (95% CI)
Subgroups, n/N (%)	10^-5 Sensitivity			10^-6 Sensitivity
Sex
Male	54/87 (62.1)	39/111 (35.1)	3.02 (1.69-5.41)	42/87 (48.3)	28/111 (25.2)	2.77 (1.52-5.04)
Female	66/110 (60)	39/87 (44.8)	1.85 (1.04-3.26)	49/110 (44.5)	26/87 (29.9)	1.88 (1.04-3.41)
Age
<70 years	59/88 (67)	36/88 (40.9)	2.94 (1.59-5.44)	44/88 (50)	25/88 (28.4)	2.52 (1.35-4.70)
≥70 years	61/109 (56)	42/110 (38.2)	2.06 (1.20-3.53)	47/109 (43.1)	29/110 (26.4)	2.12 (1.20-3.74)
Region
Europe	69/120 (57.5)	46/116 (39.7)	2.06 (1.23-3.46)	57/120 (47.5)	34/116 (29.3)	2.18 (1.28-3.73)
North America	21/37 (56.8)	13/31 (41.9)	1.82 (0.69-4.77)	14/37 (37.8)	9/31 (29)	1.49 (0.54-4.13)
Other	30/40 (75)	19/51 (37.3)	5.05 (2.03-12.60)	20/40 (50)	11/51 (21.6)	3.64 (1.46-9.04)
Weight
≤65 kg	40/58 (69)	22/63 (34.9)	4.14 (1.94-8.86)	31/58 (53.4)	18/63 (28.6)	2.87 (1.35-6.09)
>65-85 kg	58/101 (57.4)	31/88 (35.2)	2.48 (1.38-4.47)	45/101 (44.6)	19/88 (21.6)	2.92 (1.54-5.54)
>85 kg	22/38 (57.9)	25/47 (53.2)	1.21 (0.51-2.87)	15/38 (39.5)	17/47 (36.2)	1.15 (0.48-2.78)
ISS staging
I	45/68 (66.2)	30/68 (44.1)	2.48 (1.24-4.96)	32/68 (47.1)	22/68 (32.4)	1.86 (0.93-3.73)
II	47/73 (64.4)	29/75 (38.7)	2.87 (1.47-5.59)	37/73 (50.7)	17/75 (22.7)	3.51 (1.73-7.13)
III	28/56 (50)	19/55 (34.5)	1.89 (0.88-4.07)	22/56 (39.3)	15/55 (27.3)	1.73 (0.78-3.84)
Cytogenetic risk
High risk	12/25 (48)	15/27 (55.6)	0.74 (0.25-2.20)	8/25 (32)	12/27 (44.4)	0.59 (0.19-1.83)
Standard risk	95/149 (63.8)	57/149 (38.3)	2.84 (1.78-4.54)	71/149 (47.7)	37/149 (24.8)	2.76 (1.69-4.50)
ECOG PS score
0	41/71 (57.7)	36/84 (42.9)	1.82 (0.96-3.45)	28/71 (39.4)	27/84 (32.1)	1.37 (0.71-2.66)
≥1	79/126 (62.7)	42/114 (36.8)	2.88 (1.71-4.87)	63/126 (50)	27/114 (23.7)	3.22 (1.85-5.61)
Abbreviations: CI, confidence interval; CR, complete response; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; MRD, minimal residual disease; OR, odds ratio; VRd, bortezomib + lenalidomide + dexamethasone.

DARZALEX FASPRO Phase 2 Study

PLEIADES (MMY2040; NCT03412565) is an ongoing, phase 2, non-randomized, open-label, multicenter study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with various treatment regimens in patients with MM. Chari et al (2021)¹⁴ presented updated safety and efficacy results of the D-VRd, DARZALEX FASPRO in combination with bortezomib, melphalan, and prednisone (D-VMP), and DARZALEX FASPRO in combination with lenalidomide and dexamethasone (D-Rd) arms in the PLEIADES study.¹¹^-¹⁴ Results specifically to the D-VRd cohort are summarized below.

Results: D-VRd

Baseline patient and disease characteristics are presented in Table: Baseline Demographics and Patient Characteristics.
Patient disposition and exposure are summarized in Table: Patient Disposition and Exposure.

Baseline Demographics and Patient Characteristics^a,¹⁴

	Transplant-eligible NDMM
	D-VRd (n=67)
Age, years
Median (range)	59 (33-76)
18 to <65, n (%)	54 (80.6)
65 to <75, n (%)	12 (17.9)
≥75, n (%)	1 (1.5)
Male, n (%)	48 (71.6)
Median (range) body weight, kg	77 (43-148)
Race, n (%)
White	38 (56.7)
Black or African American	5 (7.5)
Asian	0 (0)
ECOG PS score, n (%)
0	40 (59.7)
1	26 (38.8)
2	1 (1.5)
Median (range) number of prior lines of therapy, n	N/A
ISS staging^b,n (%)
I	30 (44.8)
II	23 (34.3)
III	14 (20.9)
Cytogenetic risk^c,d
N	53
Standard risk, n (%)	40 (75.5)
High risk, n (%)	13 (24.5)
t(4;14)	9 (17)
t(14;16)	1 (1.9)
del17p	5 (9.4)
Abbreviations: D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; NDMM, newly diagnosed multiple myeloma. ^aAll-treated population, defined as patients who received ≥1 dose of study treatment. ^bBased on the combination of serum β2-microglobulin and albumin at screening. ^cBased on fluorescence in situ hybridization or karyotyping testing conducted locally. ^dHigh cytogenetic risk was defined as having ≥1 of t(4;14), t(14;16) or del17p abnormalities.

Patient Disposition and Exposure^a,¹⁴

	Transplant-eligible NDMM
	D-VRd (n=67)
Median treatment cycles (range), n	4 (1-4)
Median duration of treatment (range), months	2.6 (0-4)
Relative dose intensity, median %
DARZALEX FASPRO	100
Bortezomib	97.9
Melphalan	-
Prednisone	-
Lenalidomide	100
Dexamethasone	100
Abbreviations: D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; NDMM, newly diagnosed multiple myeloma. ^aThe all-treatedpopulation included all patients who received ≥1 dose of study treatment.

Efficacy

Median follow-up was 3.9 months for D-VRd cohort.
Primary endpoints were met for the D-VRd cohort with available data and response rates were similar to DARZALEX studies in GRIFFIN².
In the D-VRd cohort (n=67):
- ≥VGPR was 71.6% vs 71.7% in the GRIFFIN study.²
- ORR was 97% vs 98%
- PR was 25.4% vs 26.3%
- CR was 7.5% vs 12.1%
- sCR was 9% vs 7.1%

Pharmacokinetics

Overall, trough level or trough concentration (C_trough) and immunogenicity values were consistent with historical DARZALEX data.
C_max after the 1^st dose was D-VRd: 100 ± 48.5 µg/mL.
Sixteen patients developed rHuPh20 antibodies (all were non-neutralizing).
No patients developed anti-daratumumab antibodies.

Safety

Treatment discontinuation due to TEAEs were 2% in the D-VRd arm. A summary of TEAEs reported in each cohort is presented in Table: Safety Summary.
Any-grade IRRs occurred in 7.5% of patient across all cohorts.

Safety Summary¹⁴

	Transplant-eligible NDMM
	D-VRd (n=67)
Any TEAE, n (%)	67 (100)
Serious	19 (28.4)
Grade 3/4	39 (58.2)
Grade 5	1 (1.5)
TEAEs leading to treatment discontinuation	1 (1.5)
Abbreviations: D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; NDMM, newly diagnosed multiple myeloma; TEAE, treatment emergent adverse event.

Across all 3 cohorts with available data any grade IRRs occurred in 7.5% (15/199) of patients. IRRs were mild (grade 1/2), one patient had grade 3 IRR and no patients reported grade 4 IRR.
Median time to onset of IRRs was 4.4 hours in the D-VRd cohort.
Across all 3 cohorts with available data local injection site reactions occurred in 7.5% (15/199) of patient (all grade 1/2).
A summary of most common TEAEs is presented in Table: Most Common TEAEs (≥5% in D-VRd cohort).

Most common TEAEs (≥5% in D-VRd cohort)^a,¹⁴

Event, n (%)	Transplant-eligible NDMM
Event, n (%)	D-VRd (n=67)
Neutropenia	19 (28.4)
Lymphopenia	11 (16.4)
Thrombocytopenia	10 (14.9)
Leukopenia	5 (7.5)
Anemia	3 (4.5)
Pneumonia	2 (3)
Hypertension	1 (1.5)
Hyperglycemia	1 (1.5)
Hypokalemia	0 (0)
Any-Grade IRR	6 (9)
Abbreviations: D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; IRR, infusion-related reaction; NDMM, newly diagnosed multiple myeloma; TEAE, treatment-emergent adverse event. ^aThe all-treatedpopulation included all patients who received ≥1 dose of study treatment.

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 17 April 2025.

References

Show

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26	Zweegman S, Usmani SZ, Hungria V, et al. The phase 3 CEPHEUS trial of daratumumab plus bortezomib, lenalidomide, and dexamethasone in patients with transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: frailty subgroup analysis. Oral Presentation presented at: The 6th European Myeloma Network (EMN) Meeting; April 10-12, 2025; Athens, Greece.
27	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.
28	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: Virtual 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual.
29	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.
30	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.
31	Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Supplement to: Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2023.

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