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DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)

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DARZALEX + DARZALEX FASPRO - Minimal Residual Disease in Clinical Trials

Last Updated: 06/04/2025

SUMMARY

  • Janssen does not recommend the use of DARZALEX or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.

DARZALEX

  • CASSIOPEIA: phase 3 study evaluating the safety and efficacy of DARZALEX + bortezomib, thalidomide, and dexamethasone (D-VTd) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM).1,2
    • Moreau et al (2024)3 reported long-term outcomes of the CASSIOPEIA study after a median follow-up duration of 80.1 months from the first randomization and at a median follow-up duration of 70.6 months from the second randomization. At any time point in the D-VTd cohort, minimal residue disease (MRD)-negativity at 10-5 sensitivity threshold was achieved by 65.1% of patients in the DARZALEX subgroup and by 58.1% of patients in the observation subgroup (P=0.080), respectively; and MRD-negativity at 10-6 sensitivity threshold was achieved by 58.1% of patients in the DARZALEX subgroup and by 48.9% of patients in the observation subgroup (P=0.031), respectively. At any time point in the VTd cohort, MRD-negativity at 10-5 sensitivity threshold was achieved by 53.5% of patients in the DARZALEX subgroup and by 36.3% of patients in the observation subgroup (P=0.0001), respectively; and MRD-negativity at 10-6 sensitivity threshold was achieved by 43.7% of patients in the DARZALEX subgroup and by 26.5% of patients in the observation subgroup (P<0.0001), respectively.
    • Corre et al (2025)4 reported results on the long-term MRD status and progression-free survival (PFS) outcomes based on the MRD status from the CASSIOPEIA study after a median follow-up of 80.1 months. The overall MRD-negativity rate (10-5) improved with DARZALEX during post-induction (D-VTd vs VTd: 34.6% vs 23.1%, respectively [odds ratio [OR], 1.76; P<0.0001]) and post-consolidation (D-VTd vs VTd: 63.7% vs 43.7%, respectively [OR, 2.26; P<0.0001]). The overall MRD-negativity rate (10-5 and 10-6) was significantly (P<0.0001) higher in the DARZALEX maintenance group vs the observation group and was the highest among patients who received DARZALEX in both the induction/consolidation and maintenance phases. During post-induction, patients with MRD-negativity showed a longer PFS as compared with patients with MRD-positivity (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.32-0.49; P<0.0001). PFS improved with DARZALEX maintenance (HR, 0.63; 95% CI, 0.42-0.96; P=0.0294) vs observation (HR, 0.40; 95% CI, 0.28-0.59; P<0.0001) irrespective of whether MRD-negativity was achieved post-induction/consolidation.
  • MAIA: phase 3 study evaluating the safety and efficacy of DARZALEX in combination with lenalidomide and dexamethasone (D-Rd) compared to Rd in transplant-ineligible NDMM patients.5
    • Facon et al (2025)6 reported the updated efficacy and safety results from the MAIA study at a long-term median follow-up of 64.5 months. As of the clinical cutoff date of October 21, 2021, the D-Rd vs Rd arm showed a significantly higher (all P<0.0001) MRD-negativity (10-5 sensitivity) rate (32.1% [n=118] vs 11.1% [n=41]) and sustained MRD-negativity rate (≥12 months: 18.8% [n=69] vs 4.1% [n=15]; ≥18 months: 16.8% [n=62] vs 3.3% [n=12]).
    • Moreau et al (2025)7 reported the efficacy and safety results in clinically important subgroups of patients from the MAIA study. Treatment with D-Rd generally resulted in a greater improvement in MRD-negativity (10-5) rate, and sustained MRD-negativity (10-5) rate for ≥12 months across subgroups, compared with Rd.
  • ALCYONE: phase 3 study evaluating the safety and efficacy of DARZALEX, bortezomib, melphalan, and prednisone (D-VMP) and bortezomib, melphalan, and prednisone (VMP) in NDMM patients ineligible for high-dose chemotherapy with autologous stem-cell transplantation (ASCT).8
    • Mateos et al (2025)9 reported the final efficacy and safety analysis results of the ALCYONE study at a median follow-up of 86.7 months (interquartile range [IQR], 28.5-85.2). D-VMP vs VMP group showed a significantly higher MRD-negativity (10-5 sensitivity) rate (28% vs 7%, respectively [OR, 5.23; 95% CI, 3.27-8.36; P<0.0001]) and durable MRD-negativity (10-5) rate (≥6 months: 16% vs 4%,respectively [OR, 4.05; 95% CI, 2.27-7.21; P<0.0001]; ≥12 months: 14% vs 3%, respectively [OR, 5.63; 95% CI, 2.80-11.31; P<0.0001]).
    • San-Miguel et al (2022)10 evaluated the predictive and prognostic role of MRD-negativity and durability in patients treated in the ALCYONE study. The MRD-negativity (10-5 sensitivity) rates for D-VMP vs VMP were 26.9% vs 7% (P<0.0001) in the ITT population, and 58.8% vs 27.8% (P<0.0001) in patients who achieved ≥CR.
  • GRIFFIN: phase 2 study evaluating the safety and efficacy of D-VRd in patients with NDMM eligible for high-dose therapy (HDT) and ASCT.11
    • Part 1: Voorhees et al (2021)12 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, 50% of patients were MRD-negative (10-5 sensitivity threshold). After maintenance, 81.3% of patients were MRD-negative (10-5 sensitivity threshold).
    • Part 2: Voorhees et al (2023)13 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. At the end of the study, 14% (n/N=15/104) and 10% (n/N=10/103) of patients in the D-VRd and bortezomib, lenalidomide, and dexamethasone (VRd) arms, respectively, who were previously MRD-positive at the end of the consolidation phase, converted to MRD-negative (10-5 sensitivity).
  • POLLUX: phase 3 study evaluating the safety and efficacy of D-Rd vs Rd in patients with relapsed or refractory multiple myeloma (RRMM).14
    • Dimopoulos et al (2023)15 reported the updated efficacy and safety results of the POLLUX study at a median follow-up of 79.7 months. The MRD-negativity rate (10-5 sensitivity) in the D-Rd vs Rd arm was 33.2% vs 6.7%, respectively (P<0.0001).
  • CASTOR: phase 3 study evaluating the safety and efficacy of bortezomib and dexamethasone (Vd) alone and DARZALEX + Vd (D-Vd) in patients with RRMM.16
    • Sonneveld et al (2022)17 reported updated efficacy and safety results from CASTOR at a median follow-up of 72.6 months. The MRD-negativity rates (10-5 sensitivity) were for D-Vd vs Vd were 15.1% vs 1.6%, respectively.
  • CANDOR: phase 3 study evaluating the efficacy and safety of DARZALEX use in combination with carfilzomib and dexamethasone (D-Kd) vs Kd in patients with RRMM.18
    • Usmani et al (2023)19 reported the final efficacy and safety results of the CANDOR study after a median follow-up of approximately 50 months. The MRD-negativity rate was 18.3% in the D-Kd arm and 5.2% in the Kd arm.

DARZALEX FASPRO

  • PERSEUS: ongoing 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 daratumumab (D-R) in D-VRd group or lenalidomide (R) in VRd group in patients with NDMM eligible for ASCT.20
    • Sonneveld et al (2023)20 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), overall MRD-negativity of 75.2% vs 47.5% (P<0.0001) was higher with D-VRd vs VRd cohort.
    • Bertamini et al (2024)21 presented results from the PERSEUS study that highlighted the significance of circulating tumor cells (CTCs) as a biomarker in transplant-eligible NDMM patients. D-VRd vs VRd significantly improved patient outcomes, across both high and low CTC levels (P<0.0001). D-VRd vs VRd improved MRD-negativity rates (≥CR; 10-5 and 10-6 sensitivities) and sustained MRD-negativity rates (≥CR; 10-5 and 10-6 sensitivities; ≥12 months) in patients with both high and low CTC levels. D-VRd vs VRd improved PFS in patients with high cytogenetic risk and low CTC levels. However, there was no improvement in outcomes for patients with high cytogenetic risk combined with high CTC levels. Further, D-VRd vs VRd significantly improved PFS in patients with both high and low CTC levels (P<0.0001).
  • APOLLO: phase 3 study evaluating the safety and efficacy of DARZALEX FASPRO + pomalidomide and dexamethasone (D-Pd) vs Pd in patients with RRMM.
    • Dimopoulos et al (2021)22 reported the primary analysis of this ongoing study with a median follow-up of 16.9 months. MRD-negativity rate was 9% in patients treated with D-Pd vs 2% with Pd (OR, 4.7; 95% CI, 1.3-16.9; P=0.010).
  • 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.
    • Chari et al (2021)23 presented updated safety and efficacy results of the PLEIADES study with a median follow-up of 3.9 months for D-VRd (primary analysis), 14.3 months for D-VMP, and 14.7 months for D-Rd. MRD-negativity rates were 16.4% (90% CI, 9.4-25.7) in the D-VMP cohort and 15.4% (90% CI, 8.6-24.7) in the D-Rd cohort.
    • Moreau et al (2020)24 presented updated safety and efficacy results of the PLEIADES study with a median follow-up of 9.2 months for D-Kd (primary analysis), 25.7 months for D-Rd, and 25.2 months for D-VMP.
  • AURIGA: ongoing phase 3 study evaluating the conversion rate to MRD-negativity after maintenance treatment with DARZALEX FASPRO in combination with lenalidomide (D-R) vs lenalidomide (R) alone in patients with NDMM who are anti-cluster of differentiation (CD) 38 naïve, have a very good partial response or better (≥VGPR), and are MRD-positive following ASCT after standard-of-care induction/consolidation.25-27
    • Badros et al (2024)25,26,28 reported primary results from the phase 3 AURIGA study. The MRD-negativity (10-5 sensitivity) conversion rate by 12 months from initiation of maintenance (primary endpoint), was significantly higher for D-R vs R (50.5% vs 18.8%; OR, 4.51; 95% CI, 2.37-8.57; P<0.0001). Similarly, the MRD-negativity (10-6) conversion rate by 12 months from initiation of maintenance was higher with D-R vs R (23.2% vs 5%; OR, 5.97; 95% CI, 2.15-16.58; P=0.0002). At a median follow-up of 32.3 months, the D-R vs R arm showed a higher overall MRD-negativity conversion rate (10-5 sensitivity, 60.6% vs 27.7%; 10-6 sensitivity, 36.4% vs 12.9%).
  • 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).29-31
    • Usmani et al (2025)31 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).
    • Zweegman et al (2024)32 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.
    • Zweegman et al (2025)33 presented a subgroup analysis to assess efficacy and safety outcomes from the CEPHEUS study based on frailty status in patients with NDMM who were TIE or transplant deferred. The overall MRD-negativity rates (at
    • 10-5 and 10-6 threshold) and sustained (≥12 months) MRD-negativity rates (10-5 threshold) were higher with D-VRd compared with VRd across the International Myeloma Working Group (IMWG) and Intergroupe Francophone de Myélome (IFM) frailty subgroups. A reduction in the risk of progression or death with D-VRd was reported to be 41% and 44% in the IMWG fit and intermediate-fit groups, and 42% and 49% in the IFM nonfrail and frail groups, respectively. Any grade 3/4 events reported in the D-VRd vs VRd arms were 89.5% vs 84.1% in the IMWG fit subgroup, 97.3% vs 88.9% in the IMWG intermediate fitness subgroup, 90.0% vs 84.6% in the IFM nonfrail subgroup, and 98.2% vs 89.7% in the IFM frail subgroup. Overall safety was consistent with the established profiles of DARZALEX FASPRO and VRd across frailty subgroups, with no detriment in health-related quality of life (HRQoL).
  • Several subgroup analyses that reported on MRD outcomes with the use of DARZALEX or DARZALEX FASPRO were identified. These analyses are listed in the References section for your information.7,34-46

PRODUCT LABELING

CLINICAL DATA

DARZALEX in Combination with Bortezomib, Thalidomide, and Dexamethasone in Previously Untreated MM

CASSIOPEIA (MMY3006; NCT02541383) is an ongoing, open-label, 2-arm, multicenter, randomized, phase 3 study evaluating the safety and efficacy of D-VTd in patients with NDMM who are eligible for high-dose chemotherapy and ASCT.1,2

Long-term Follow-up in CASSIOPEIA Study.

Moreau et al (2024)3 reported long-term outcomes of the CASSIOPEIA study after a median follow-up duration of 80.1 months from the first randomization and at a median follow-up duration of 70.6 months from the second randomization.

Study Design

  • This planned analysis represents the study's conclusion with the final data cutoff of September 1, 2023. During the induction and consolidation phases, efficacy assessments were conducted on the ITT population cohort, encompassing all patients from the first randomization. In the maintenance phase, efficacy analyses were performed on the maintenance-specific ITT population, including patients randomized during the second randomization.

Results

Patient Disposition
  • Between September 22, 2015, and August 1, 2017, a total of 1085 patients were enrolled and randomized to receive D-VTd (n=543) and VTd (n=542).
  • Overall, 458 patients (84%) in the D-VTd group and 428 patients (79%) in the VTd group, who completed consolidation and achieved a partial response or better (≥PR), were re-randomized to either DARZALEX maintenance (n=442) or observation (n=444).
    • At a clinical data cutoff of September 1, 2023, 339 patients (77%) had completed DARZALEX maintenance, and 317 patients (71%) had completed observation during the maintenance phase.
    • A total of 61 patients (14%) in the DARZALEX maintenance group and 118 patients (27%) in the observation group had discontinued treatment due to disease progression during the maintenance phase.
Efficacy

The accumulative MRD-negativity rate was calculated as the proportion of patients achieving MRD-negativity before a set timepoint, compared within the maintenance ITT population, stratified by the study site, ISS disease stage, and cytogenetic risk status.PFS in MRD-Positive/MRD-Negative Subgroups47
Subgroup
DARZALEX
Observation
HR (95% CI)
n/N
Median PFS, Months
n/N
Median PFS, Months
All patients in the maintenance-specific ITT population
186/442
NE
279/444
45.8
0.54 (0.45-0.65)
MRD
   MRD-positive
66/105
46.5
95/107
24.2
0.44 (0.32-0.60)
   MRD-negative
120/337
NE
184/337
61.1
0.55 (0.40-0.70)
Abbreviations: CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; MRD, minimal residual disease; NE, not estimable; PFS, progression-free survival.

Proportion of Patients With a ≥CR and Sustained MRD-Negativity at Any Timepoint From Post-induction Onwards in the Maintenance-Specific ITT Population3
MRD- Negativity Sensitivity Threshold
D-VTd
OR
(95% CI)
P Value
VTd
OR
(95% CI)
P Value
DARZALEX
(n=229)
Obs
(n=229)
DARZALEX
(n=213)
Obs
(n=215)
At any time point
   10-5, %
65.1
58.1
1.47
(0.95-2.26)
0.080
53.5
36.3
2.33
(1.51-3.60)
0.0001
   10-6, %
58.1
48.9
1.56
(1.04-2.34)
0.031
43.7
26.5
2.44
(1.56-3.81)
<0.0001
≥12 Months
   10-5, %
56.3
46.3
1.61
(1.08-2.41)
0.020
44.1
24.7
2.71
(1.73-4.23)
<0.0001
   10-6, %
47.6
36.2
1.68
(1.13-2.50)
0.0096
31.9
14.9
2.92
(1.77-4.82)
<0.0001
≥24 Months
   10-5, %
49.8
36.7
1.82
(1.23-2.71)
0.0028
36.2
16.7
3.15
(1.94-5.12)
<0.0001
   10-6, %
41
27.9
1.87
(1.25-2.81)
0.0023
24.9
10.2
3.11
(1.78-5.44)
<0.0001
Abbreviations: CI, confidence interval; CR, complete response; D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; ITT, intent-to-treat; MRD, minimal residual disease; Obs, observation; OR, odds ratio; VTd, bortezomib + thalidomide + dexamethasone.

MRD-Negativity Rates at 10-5 Sensitivity Threshold Following Induction and Consolidation in the ITT Population47
Post-Induction
Post-Consolidation
D-VTd
(n=543)
VTd
(n=542)
D-VTd
(n=543)
VTd
(n=542)
MRD-negativity rate, %
9.2
5.4
33.7
20.3
   P value
0.015
<0.0001
Abbreviations: D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; ITT, intent-to-treat; MRD, minimal residual disease; VTd, bortezomib + thalidomide + dexamethasone.

Safety

  • Summary of causes of death during and after the maintenance phase and SPMs by induction/consolidation treatment in the maintenance-specific safety population of the MAIA study have been reported by Moreau et al (2024)3.

Corre et al (2025)4 reported results on the long-term MRD status and PFS outcomes based on the MRD status from the CASSIOPEIA study after a median follow-up of 80.1 months.

Study Design/Methods

  • Patients were randomly assigned (1:1) to receive D-VTd or VTd for induction/consolidation. Patients were randomized to the maintenance phase to undergo DARZALEX maintenance or observation for 2 years. The MRD status was assessed at predefined timepoints during each study phase.
  • During maintenance, MRD analyses were conducted in patients who achieved a very good partial response (VGPR) or ≥VGPR at 6, 12, and 24 months of maintenance or observation.
  • During follow-up, MRD analyses were performed at 1, 2, and 3 years in patients who did not progress and were MRD-negative after 24 months of maintenance vs observation or at their last assessment since day 100 post-ASCT.
  • The sustained MRD-negativity rate was determined by a consistent result of MRD-negativity (with no MRD-positive result between the measurements) for a given length of time (minimum of 12 months, with measurements up to ≥36 months), as observed at any timepoint between postinduction and the end of follow-up; it was compared across treatment arms, stratified by the depth of response.
  • The accumulative MRD-negativity rate was calculated as the proportion of patients achieving MRD-negativity before a set timepoint, compared within the maintenance ITT (mITT) population, stratified by the study site, ISS disease stage, and cytogenetic risk status.

Results

Efficacy

MRD-Negativity Rates at Any Time During Maintenance and Follow-up in the mITT Population4,48
MRD-Negativity Sensitivity Threshold
D-VTd
OR
P Value
VTd
OR
P Value
DARZALEX
(n=229)
Obs
(n=229)
DARZALEX
(n=213)
Obs
(n=215)
Overall MRD-negativitya, %
   10-5
77.3
70.7
1.76
0.0417
70.9
51.2
3.16
<0.0001
   10-6
60.7
52
1.55
0.0365
48.4
30.7
2.41
<0.0001
At 6 monthsb, %
   10-5
59.4
53.3
1.27
0.2132
48.8
34.4
1.78
0.0043
   10-6
38.4
36.7
1.06
0.7662
27.2
19.5
1.58
0.0550
At 12 monthsb, %
   10-5
61.6
55.9
1.23
0.2667
48.8
33.0
1.92
0.0012
   10-6
39.3
34.9
1.17
0.4372
31.9
18.1
2.09
0.0013
At 24 months, %b
   10-5
62.9
50.7
1.62
0.0121
49.3
21.4
3.47
<0.0001
   10-6
46.3
31.4
1.81
0.0024
32.9
13.0
3.49
<0.0001
MRD-negativity conversion ratec, %
   10-5
36.7
25.0
1.74
0.1540
47.4
9.9
8.22
<0.0001
Abbreviations: D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; mITT, maintenance intent-to-treat; MRD, minimal residual disease; Obs, observation; OR, odds ratio; VTd, bortezomib + thalidomide + dexamethasone.
aPost-consolidation after the second randomization.
bmITT population.
cPercentages were calculated with the number of patients with a post-consolidation MRD-positive status in each treatment group as the denominator (D-VTd/DARZALEX, n=60;  D-VTd/Obs, n=68; VTd/DARZALEX, n=97; VTd/Obs, n=91).

MRD-Negativity With ≥CR Rates at Defined Time Points During Maintenance in the mITT Population4
MRD-Negativity Sensitivity Threshold
D-VTd
OR
P Value
VTd
OR
P Value
DARZALEX
(n=229)
Obs
(n=229)
DARZALEX
(n=213)
Obs
(n=215)
At 6 months, %
   10-5
57.2
50.2
1.30
0.1750
44.1
29.8
1.85
0.0027
   10-6
37.6
35.8
1.06
0.7848
25.8
18.1
1.59
0.0541
At 12 months, %
   10-5
59.4
52.0
1.31
0.1541
47.4
30.2
2.08
0.0004
   10-6
38.9
34.5
1.18
0.4178
31.5
16.7
2.25
0.0005
At 24 months, %
   10-5
60.3
47.2
1.66
0.0081
47.4
20.5
3.41
<0.0001
   10-6
45.9
31.0
1.83
0.0021
31.9
12.6
3.47
<0.0001
Abbreviations: CR, complete response; D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; mITT, maintenance intent-to-treat; MRD, minimal residual disease; Obs, observation; OR, odds ratio; VTd, bortezomib + thalidomide + dexamethasone.

Accumulative MRD-Negativity Rates in the mITT Population Over Time4
MRD-Negativity Sensitivity Threshold
D-VTd
VTd
DARZALEX
(n=229)
Obs
(n=229)
DARZALEX
(n=213)
Obs
(n=215)
MRD-negativity rate, %
   At day 28
      10-5
31.0
28.8
23.9
16.3
      10-6
8.7
9.2
8.5
4.7
   At day 100a
      10-5
68.1
64.2
47.4
51.2
      10-6
32.8
31.0
19.7
18.6
   At week 25
      10-5
74.2
68.6
61.5
55.3
      10-6
46.7
44.5
32.9
26.5
   At week 52
      10-5
75.1
71.6
66.7
57.7
      10-6
52.8
48.5
41.3
28.8
   At week 105
      10-5
77.7
73.8
71.4
58.1
      10-6
58.5
51.5
47.4
31.6
   At 12 monthsb
      10-5
79.0
74.2
73.2
58.1
      10-6
59.4
53.3
47.4
28.8
   At 24 monthsb
      10-5
79.0
74.2
73.2
58.1
      10-6
60.3
53.3
48.8
32.1
   At 36 monthsb
      10-5
79.0
74.2
73.2
58.1
      10-6
60.7
53.3
48.8
32.1
Abbreviations: D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; mITT, maintenance intent-to-treat; MRD, minimal residual disease; Obs, observation; VTd, bortezomib + thalidomide + dexamethasone.
aPost autologous stem cell transplantation.
bPre-progressive disease follow-up.

Accumulative MRD-Negativity With ≥CR Rates in the mITT Population Over Time4
MRD-Negativity Sensitivity Threshold
D-VTd
VTd
DARZALEX
(n=229)
Obs
(n=229)
DARZALEX
(n=213)
Obs
(n=215)
MRD-negativity with ≥CR, %
   At day 28
      10-5
28.4
27.9
22.1
12.6
      10-6
8.3
9.2
7.5
4.2
   At day 100a
      10-5
63.8
60.3
42.7
40.9
      10-6
31.9
30.6
17.8
17.2
   At week 25
      10-5
68.6
63.8
54.0
42.8
      10-6
45.9
43.2
31.0
23.7
   At week 52
      10-5
69.4
65.1
58.7
45.1
      10-6
52.0
46.7
39.0
25.1
   At week 105
      10-5
71.6
66.4
63.4
45.6
      10-6
57.6
49.8
44.6
26.0
   At 12 monthsb
      10-5
72.1
66.4
63.8
45.6
      10-6
58.5
51.1
44.6
27.9
   At 24 monthsb
      10-5
72.1
66.4
63.8
45.6
      10-6
59.4
51.1
46.0
28.4
   At 36 monthsb
      10-5
72.1
66.4
63.8
45.6
      10-6
59.8
51.1
46.0
28.4
Abbreviations: CR, complete response; D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; mITT, maintenance intent-to-treat; MRD, minimal residual disease; Obs, observation; VTd, bortezomib + thalidomide + dexamethasone.
aPost autologous stem cell transplantation.
bPre-progressive disease follow-up.

Sustained MRD-Negativity Rates at Any Time During the Study – mITT Population4
Sustained MRD-Negativity Sensitivity Threshold
D-VTd
OR
P Value
VTd
OR
P Value
DARZALEX
(n=229)
Obs
(n=229)
DARZALEX
(n=213)
Obs
(n=215)
At ≥12 months, %
   10-5
65.5
57.2
1.59
0.0369
50.7
32.1
2.53
<0.0001
   10-6
49.3
37.1
1.75
0.0053
32.4
15.3
2.89
<0.0001
At ≥24 months, %
   10-5
58.5
46.7
1.78
0.0056
43.7
20.9
3.50
<0.0001
   10-6
41.9
28.4
1.91
0.0017
25.4
10.2
3.20
<0.0001
At ≥36 months, %
   10-5
43.7
32.3
1.70
0.0088
31.9
12.1
3.79
<0.0001
   10-6
29.7
22.7
1.46
0.0821
19.7
6.5
3.74
<0.0001
Abbreviations: D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; mITT, maintenance intent-to-treat; MRD, minimal residual disease; Obs, observation; OR, odds ratio; VTd, bortezomib + thalidomide + dexamethasone.

Sustained MRD-Negativity With ≥CR Rates at Any Time During the Study - mITT Population4
Sustained MRD-Negativity Sensitivity Threshold
D-VTd
OR
P Value
VTd
OR
P Value
DARZALEX
(n=229)
Obs
(n=229)
DARZALEX
(n=213)
Obs
(n=215)
At ≥12 months, %
   10-5
63.3
53.7
1.66
0.0191
48.8
29.3
2.64
<0.0001
   10-6
47.6
36.2
1.68
0.0096
31.9
14.9
2.92
<0.0001
At ≥24 months, %
   10-5
57.6
44.5
1.88
0.0022
42.7
20.0
3.54
<0.0001
   10-6
41.0
27.9
1.87
0.0023
24.9
10.2
3.11
<0.0001
At ≥36 months, %
   10-5
43.2
31.0
1.78
0.0047
31.5
11.6
3.87
<0.0001
   10-6
29.3
22.3
1.47
0.0807
19.7
6.5
3.74
<0.0001
Abbreviations: CR, complete response; D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; mITT, maintenance intent-to-treat; MRD, minimal residual disease; Obs, observation; OR, odds ratio; VTd, bortezomib + thalidomide + dexamethasone.

MRD-Negativity Rates Based on the Cytogenetic Risk Status - ITT Population48
MRD-Negativity Status
Standard Risk
P Value
High Risk
P Value
D-VTd
(n=460)
VTd
(n=454)
D-VTd
(n=82)a
VTd
(n=86)a
10-5, %
66.1
45.8
<0.0001
62.2
47.7
0.0595
Abbreviations: D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; ITT, intent-to-treat; MRD, minimal residual disease; VTd, bortezomib + thalidomide + dexamethasone.
aAmong patients with high cytogenetic risk, 40 (49%) patients in the D-VTd group and 47 (55%) patients in the VTd group had a t(4;14) abnormality only, 31 (38%) patients in the D-VTd group and 33 (38%) patients in the VTd group had a del(17p) abnormality only, and 11 (13%) patients in the D-VTd group and 6 (7%) patients in the VTd group had both t(4;14) and del(17p) abnormalities. High cytogenetic risk was a stratification factor for the induction/consolidation phase (Part 1).

MRD-Negativity Rates Based on the Revised ISS Stage - ITT Population48
MRD-Negativity Status
ISS I
P Value
ISS II
P Value
ISS III
P Value
D-VTd
(n=103)
VTd
(n=146)
D-VTd
(n=383)
VTd
(n=344)
D-VTd
(n=49)
VTd
(n=50)
10-5, %
69.9
42.5
<0.0001
64.2
47.7
<0.0001
63.3
48.0
0.1284
Abbreviations: D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; VTd, bortezomib + thalidomide + dexamethasone.

MRD-Negativity Rates Based on the Cytogenetic Risk Status - mITT Population48
MRD-Negativity Sensitivity Threshold
Standard Risk
P Value
High Risk
P Value
DARZALEX
(n=383)
Obs
(n=374)
DARZALEX
(n=57)a
Obs
(n=70)a
Overall MRD-negativityb, %
   10-5
73.4
61.8
0.0007
78.9
58.6
0.0150
   10-6
52
42
0.0060
73.7
40
0.0002
≥12 months of sustained MRD-negativityc, %
   10-5
56.4
46.0
0.0042
70.2
40.0
0.0007
   10-6
38.6
28.9
0.0045
57.9
14.3
<0.0001
Abbreviations: mITT, maintenance intent-to-treat; MRD, minimal residual disease; Obs, observation.
aAmong patients with high cytogenetic risk, 34 (60%) patients in the DARZALEX group and 34 (49%) patients in the Obs group had a t(4;14) abnormality only, 21 (37%) patients in the DARZALEX group and 29 (41%) patients in the Obs group had a del(17p) abnormality only, and 2 (3%) patients in the DARZALEX group and 7 (10%) patients in the Obs group had both t(4;14) and del(17p) abnormalities. High cytogenetic risk was not a stratification factor for the maintenance phase (Part 2). When broken down by induction treatment arm, among patients with high cytogenetic risk, 19 (61%) patients in the D-VTd/DARZALEX group, 14 (42%) patients in the D-VTd/Obs group, 15 (58%) patients in the VTd/DARZALEX group, and 20 (54%) patients in the D-VTd/Obs group had a t(4;14) abnormality only; 11 (36%), 15 (46%), 10 (38%), and 14 (38%) patients, respectively, had a del(17p) abnormality only, and 1 (3%), 4 (12%), 1 (4%), and 3 (8%) patients, respectively, had both t(4;14) and del(17p) abnormalities.
bMRD-negativity in the maintenance ITT population during maintenance and follow-up.
cMRD-negativity in the maintenance ITT population from post-induction up to the end of follow-up.

MRD-Negativity Rates Based on the Revised ISS Stage - mITT Population48
MRD-Negativity Sensitivity
Threshold
ISS I
P Value
ISS II
P Value
ISS III
P Value
D-VTd
(n=105)
VTd
(n=102)
D-VTd
(n=287)
VTd
(n=310)
D-VTd
(n=44)
VTd
(n=29)
Overall MRD-negativitya, %
   10-5
74.3
65.7
0.1779
73.9
59.7
0.0002
75.0
65.5
0.3844
   10-6
48.6
42.2
0.3552
56.4
40.6
0.0001
61.4
51.7
0.4181
≥12 months of sustained MRD-negativityb, %
   10-5
59.0
45.1
0.0451
58.2
44.8
0.0011
56.8
48.3
0.4771
   10-6
41.9
30.4
0.0857
41.8
25.5
<0.0001
36.4
24.1
0.2745
Abbreviations: D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; ISS, International Staging System; mITT, maintenance intent-to-treat; MRD, minimal residual disease; VTd, bortezomib + thalidomide + dexamethasone.
aMRD-negativity in the maintenance ITT population during maintenance and follow-up.
bMRD-negativity in the maintenance ITT population from post-induction up to the end of follow-up.
  • During post-induction, patients with MRD-negativity achieved a longer PFS as compared with patients with MRD-positivity, regardless of induction/consolidation treatment (67.2% vs 35%, HR, 0.40; 95% CI, 0.32-0.49; P<0.0001).4
    • The median PFS was not reached in patients with MRD-negativity in the D-VTd group. PFS analysis results by the post-induction MRD status and the induction/consolidation arm in the ITT population are presented in Table: PFS Analysis by the Post-induction MRD Status and Induction/Consolidation Arm - ITT Population.4
    • A longer PFS was achieved by patients who were MRD-negative post-induction than that achieved by patients who were not MRD-negative until post-consolidation, regardless of induction/consolidation or a second randomization (HR, 0.54; 95% CI, 0.42-0.70; P<0.0001).4,48
    • PFS improved with DARZALEX maintenance (HR, 0.63; 95% CI, 0.42-0.96; P=0.0294) vs observation (HR, 0.40; 95% CI, 0.28-0.59; P<0.0001) irrespective of whether MRD-negativity was achieved post-induction/consolidation.48
  • Maintenance with DARZALEX improved PFS irrespective of induction/consolidation treatment and the post-consolidation MRD status.4,48
  • DARZALEX induction/consolidation improved PFS regardless of the cytogenetic risk status and revised ISS disease stage in the ITT population.4,48
  • DARZALEX maintenance improved PFS regardless of the cytogenetic risk status and revised ISS disease stage.4,48

PFS Analysis by the Post-induction MRD Status and Induction/Consolidation Arm - ITT Population4
MRD Status
72-Month
PFS Rate, %
Median, Months
HR (95% CI)
P Value
D-VTd MRD-negative
76.9
Not reached
0.40 (0.27-0.59)
<0.0001
VTd MRD-negative
52.9
77
D-VTd MRD-positive
39.7
54.1
0.74 (0.61-0.89)
0.0018
VTd MRD-positive
30.8
45.3
D-VTd MRD-negative
76.9
Not reached
0.30 (0.22-0.41)
<0.0001
D-VTd MRD-positive
39.7
54.1
VTd MRD-negative
52.9
77
0.57 (0.43-0.75)
<0.0001
VTd MRD-positive
30.8
45.3
Abbreviations: CI, confidence interval; D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; HR, hazard ratio; ITT, intent-to-treat; MRD, minimal residual disease; PFS, progression-free survival; VTd, bortezomib + thalidomide + dexamethasone.

Analysis of PFS From Second Randomization by the Post-consolidation MRD Status Regardless of Induction/Consolidation - mITT Population4
MRD Status
72-Month
PFS Rate, %
Median, Months
HR (95% CI)
P Value
DARZALEX MRD-negative
72.1
Not reached
0.54 (0.38-0.78)
0.0007
Obs MRD-negative
47.3
78.1
DARZALEX MRD-positive
52.0
66.2
0.48 (0.39-0.60)
<0.0001
Obs MRD-positive
26.2
36.6
DARZALEX MRD-negative
72.1
Not reached
0.48 (0.34-0.67)
<0.0001
DARZALEX MRD-positive
52.0
66.2
Obs MRD-negative
47.3
78.1
0.47 (0.36-0.60)
<0.0001
Obs MRD-positive
26.2
36.6
Abbreviations: CI, confidence interval; HR, hazard ratio; MRD, minimal residual disease; Obs, observation; PFS, progression-free survival.

Analysis of PFS From Second Randomization by the Post-consolidation MRD Status in the D-VTd and V-Td Treatment arms -mITT Population4
MRD Status
72-Month
PFS Rate, %
Median, Months
HR (95% CI)
P Value
D-VTd/DARZALEX MRD-negative
73.8
Not reached
0.73 (0.45-1.17)
0.1909
D-VTd/Obs MRD-negative
63.5
Not reached
D-VTd/DARZALEX MRD-positive
47.5
60.8
0.82 (0.59-1.15)
0.2471
D-VTd/Obs MRD-positive
39.9
50.0
VTd/DARZALEX MRD-negative
69.4
Not reached
0.37 (0.21-0.63)
0.0002
VTd/Obs MRD-negative
35.0
49.6
VTd/DARZALEX MRD-positive
47.7
70.7
0.32 (0.24-0.43)
<0.0001
VTd/Obs MRD-positive
13.4
26.0
Abbreviations: CI, confidence interval; D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; HR, hazard ratio; MRD, minimal residual disease; Obs, observation; PFS, progression-free survival; VTd, bortezomib + thalidomide + dexamethasone.

PFS Analysis Based on the Cytogenetic Risk Status - ITT Population48
Cytogenetic Risk Status
72-Month
PFS Rate, %
Median, Months
HR (95% CI)
P Value
D-VTd standard risk
57.0
87.3
0.60 (0.5-0.72)
<0.0001
VTd standard risk
39.7
57.8
D-VTd high risk
36.1
48.5
0.68 (0.47-0.99)
0.0410
VTd high risk
22.9
34.2
Abbreviations: CI, confidence interval; D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; HR, hazard ratio; ITT, intent-to-treat; PFS, progression-free survival; VTd, bortezomib + thalidomide + dexamethasone.

PFS Analysis Based on the R-ISS Stage in the ITT Population48
R-ISS Stage
72-Month
PFS Rate, %
Median, Months
HR (95% CI)
P Value
ITT population
   D-VTd R-ISS I
65.0
Not reached
0.49 (0.33-0.72)
0.0002
   VTd R-ISS I
36.9
60.8
   D-VTd R-ISS II
52.1
75.4
0.64 (0.52-0.77)
<0.0001
   VTd R-ISS II
37.2
51.1
   D-VTd R-ISS III
41.4
56.8
0.63 (0.39-1.02)
0.0600
   VTd R-ISS III
25.1
36.7
Abbreviations: CI, confidence interval; D-VTd, DARZALEX + bortezomib + thalidomide + dexamethasone; HR, hazard ratio; ITT, intent-to-treat; PFS, progression-free survival; R-ISS, revised International Staging System;  VTd, bortezomib + thalidomide + dexamethasone.

PFS Analysis Based on the Cytogenetic Risk Status - mITT Population4
Cytogenetic Risk Status
72-Month
PFS Rate, %
Median, Months
HR (95% CI)
P Value
DARZALEX standard riska
57.0
Not reached
0.58 (0.48-0.71)
<0.0001
Obs standard risk
39.8
49
DARZALEX high riska
54.2
Not reached
0.39 (0.25-0.63)
<0.0001
Obs high risk
19.6
27.2
DARZALEX standard riska
57.0
Not reached
0.83 (0.55-1.25)
0.3696
DARZALEX high riska
54.2
Not reached
Abbreviations: CI, confidence interval; HR, hazard ratio; mITT, maintenance intent-to-treat; Obs, observation; PFS, progression-free survival.
aDARZALEX standard risk vs DARZALEX high risk: HR, 0.83; P=0.3696.

PFS Analysis Based on the R-ISS Stage - mITT Population48
R-ISS Stage
72-Month
PFS Rate, %
Median, Months
HR (95% CI)
P Value
DARZALEX R-ISS I
58.4
Not reached
0.55 (0.37-0.82)
0.0032
Obs R-ISS I
41.9
49.1
DARZALEX R-ISS II
57.9
Not reached
0.52 (0.41-0.65)
<0.0001
Obs R-ISS II
35.5
45.2
DARZALEX R-ISS III
50.0
Not reached
0.54 (0.30-0.97)
0.0359
Obs R-ISS III
24.1
33.1
Abbreviations: CI, confidence interval; HR, hazard ratio; mITT, maintenance intent-to-treat; Obs, observation; PFS, progression-free survival; R-ISS, revised International Staging System.

DARZALEX in Combination with Lenalidomide and Dexamethasone in Patients with NDMM

MAIA (MMY3008; NCT02252172) is an international, phase 3, randomized, open-label, active-controlled, multicenter study in patients with NDMM not eligible for high-dose chemotherapy and ASCT (N=737).5 Facon et al (2025)6 reported the updated efficacy and safety results from the MAIA study at a long-term median follow-up of 64.5 months.

Study Design/Methods

  • Primary endpoint: PFS
  • Secondary endpoints: ≥CR, duration of response (DOR), ≥VGPR, MRD-negativity rate (10-5 sensitivity) via NGS, ORR, overall survival (OS), PFS2, sCR, time to next (second-line) treatment, time to response (TTR), TTP, and safety

Results

Patient Characteristics
  • A total of 737 (D-Rd, n=368; Rd, n=369) patients were randomized in this study.6
  • The median follow-up was 64.5 months (range, 0-77.6).6
  • The median treatment duration was 47.5 months (range, 0.1-77.3) vs 22.6 months (range, 0.03-77.5) in the D-Rd vs Rd arm, respectively.49 
Efficacy
  • The D-Rd vs Rd arm showed a significantly higher (all P<0.0001) MRD-negativity rate (10-5 sensitivity; 32.1% [n=118] vs 11.1% [n=41]) and sustained MRD-negativity rate (≥12 months, 18.8% [n=69] vs 4.1% [n=15]; ≥18 months, 16.8% [n=62] vs 3.3% [n=12]).6
    • The MRD-negativity response rate deepened over time, increasing from 12.8% at 12 months to 20.4% at 18 months, 24.2% at 24 months, 27.4% at 30 months, 29.3% at 36 months, 31.5% at 48 months, and 31.8% at 60 months.
    • The D-Rd vs Rd arm was associated with an increased MRD-negativity rate across all age subgroups.
      • Patients aged <70 years: 35.9% (n=28) vs 11.7% (n=9); P=0.0006
      • Patients aged ≥70 to <75 years: 36.2% (n=47) vs 12.2% (n=16); P<0.0001
      • Patients aged ≥75 years: 26.9% (n=43) vs 9.9% (n=16); P<0.0001
      • Patients aged ≥80 years: 25.8% (n=17) vs 5.6% (n=4); P=0.0016
    • PFS and OS improved in patients who achieved MRD-negativity vs those who were MRD-positive in both treatment arms, with more patients in the D-Rd arm achieving MRD-negativity.

Safety

  • Summary of any-grade (≥30%) and grade 3/4 (≥20%) treatment-emergent adverse events (TEAEs) in the safety population of the MAIA study have been reported by Facon et al (2025).6,49

Analysis of Clinically Important Subgroups of MAIA

Moreau et al (2025)7 presented the efficacy and safety results in clinically important subgroups of patients from the MAIA study.

Study Design/Methods

  • Efficacy outcomes like MRD-negativity were analyzed in subgroups based on the following patient characteristics:
    • Age ≥75 years
    • Frail (based on the simplified frailty score, which was assessed retrospectively using age, baseline ECOG PS, and Charlson comorbidity index)
    • ISS stage III disease
    • Revised ISS stage III disease
    • Renal insufficiency (baseline CrCl ≤60 mL/min)
    • Extramedullary plasmacytomas
    • Cytogenetic risk
      • Presence of HRCAs (t[4;14], t[14;16], and/or del[17p]) or a high serum lactate dehydrogenase level
      • Standard cytogenetic risk (0 of the following HRCAs: t[4;14], t[14;16], and del[17p])
      • High cytogenetic risk (≥1 of the following HRCAs: t[4;14], t[14;16], and del[17p])
      • Revised standard cytogenetic risk (0 of the following HRCAs: t[4;14], t[14;16], del[17p], t[14;20], gain[1q21], and amp[1q21])
      • Revised high cytogenetic risk (≥1 of the following HRCAs: t[4;14], t[14;16], del[17p], t[14;20], gain[1q21], and amp[1q21])
      • Gain(1q21) (3 copies of chromosome 1q21, with or without other HRCAs)
      • Amp(1q21) (≥4 copies of chromosome 1q21, with or without other HRCAs)
      • Gain(1q21) or amp(1q21) (3 or ≥4 copies of chromosome 1q21, with or without other HRCAs)
      • 1 HRCA (only 1 of the following HRCAs: t[4;14], t[14;16], del[17p], t[14;20], gain[1q21], or amp[1q21])
      • Two or more HRCAs (≥2 of the following HRCAs: t[4;14], t[14;16], del[17p], t[14;20], gain[1q21], and amp[1q21])
      • Isolated gain(1q21) (3 copies of chromosome 1q21, without any other HRCAs)
      • Isolated amp(1q21) (≥4 copies of chromosome 1q21, without any other HRCAs)
      • Isolated gain(1q21) or amp(1q21) (3 or ≥4 copies of chromosome 1q21, without any other HRCAs)
      • Gain(1q21) or amp(1q21) plus ≥1 HRCA (3 or ≥4 copies of chromosome 1q21, plus ≥1 of the following HRCAs: t[4;14], t[14;16], del[17p], and t[14;20])

Results

Patient Characteristics
  • Overall, 737 patients (D-Rd, 368; Rd, 369) were included in the ITT population.
  • The median follow-up was 64.5 months.
Efficacy

Subgroup Analysis of MRD-Negativity (10-5) Rates in the ITT Population of MAIA7
Subgroup
D-Rd
n/N (%)
Rd
n/N (%)
OR (95% CI)a
ITT (overall)
118/368 (32.1)
41/369 (11.1)
3.78 (2.55-5.59)
Patient characteristics
   Age ≥75 years
43/160 (26.9)
16/161 (9.9)
3.33 (1.79-6.21)
   Frail
44/172 (25.6)
22/169 (13.0)
2.30 (1.31-4.04)
   Renal insufficiency
48/162 (29.6)
11/142 (7.7)
5.01 (2.49-10.11)
Disease-related characteristics
   ISS stage III
29/107 (27.1)
12/110 (10.9)
3.04 (1.46-6.34)
   Revised ISS stage III
13/43 (30.2)
3/40 (7.5)
5.34 (1.39-20.50)
   Extramedullary plasmacytomas
5/15 (33.3)
0/9 (0)
NE (NE-NE)
   Cytogenetic risk
      Standard cytogenetic risk
93/271 (34.3)
33/279 (11.8)
3.89 (2.50-6.06)
      High cytogenetic risk
12/48 (25.0)
1/44 (2.3)
14.33 (1.78-115.59)
      Revised standard cytogenetic risk
60/176 (34.1)
21/187 (11.2)
4.09 (2.36-7.09)
      Revised high cytogenetic risk
49/156 (31.4)
15/152 (9.9)
4.18 (2.22-7.86)
      Gain(1q21)
19/53 (35.8)
6/44 (13.6)
3.54 (1.27-9.89)
      Amp(1q21)
23/74 (31.1)
8/76 (10.5)
3.83 (1.59-9.27)
      Gain(1q21) or amp(1q21)
42/127 (33.1)
14/120 (11.7)
3.74 (1.92-7.30)
      1 HRCA
44/137 (32.1)
15/137 (10.9)
3.85 (2.02-7.34)
      ≥2 HRCAs
5/19 (26.3)
0/15 (0)
NE (NE-NE)
      Isolated gain(1q21)
17/47 (36.2)
6/42 (14.3)
3.40 (1.19-9.71)
      Isolated amp(1q21)
20/61 (32.8)
8/65 (12.3)
3.48 (1.39-8.66)
      Isolated gain(1q21) or amp(1q21)
37/108 (34.3)
14/107 (13.1)
3.46 (1.74-6.89)
      Gain(1q21) or amp(1q21) plus
      ≥1 HRCA
5/19 (26.3)
0/13 (0)
NE (NE-NE)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; Rd, lenalidomide + dexamethasone.
aOR >1 indicates an advantage for D-Rd.

Subgroup Analysis of Rates of Sustained MRD-Negativity (10-5) Lasting ≥12 Months in the ITT Population7
Subgroup
D-Rd
n/N (%)
Rd
n/N (%)
OR (95% CI)a
ITT (overall)
69/368 (18.8)
15/369 (4.1)
5.45 (3.05-9.72)
Patient characteristics
   Age ≥75 years
22/160 (13.8)
5/161 (3.1)
4.97 (1.83-13.49)
   Frail
27/172 (15.7)
7/169 (4.1)
4.31 (1.82-10.19)
   Renal insufficiency
30/162 (18.5)
2/142 (1.4)
15.91 (3.73-67.89)
Disease-related characteristics
   ISS stage III
17/107 (15.9)
3/110 (2.7)
6.74 (1.91-23.73)
   Revised ISS stage III
7/43 (16.3)
0/40 (0)
NE (NE-NE)
   Extramedullary plasmacytomas
2/15 (13.3)
0/9 (0)
NE (NE-NE)
Cytogenetic risk
      Standard cytogenetic risk
55/271 (20.3)
11/279 (3.9)
6.20 (3.17-12.14)
      High cytogenetic risk
6/48 (12.5)
0/44 (0)
NE (NE-NE)
      Revised standard cytogenetic risk
31/176 (17.6)
5/187 (2.7)
7.78 (2.95-20.52)
      Revised high cytogenetic risk
32/156 (20.5)
7/152 (4.6)
5.35 (2.28-12.53)
      Gain(1q21)
14/53 (26.4)
3/44 (6.8)
4.91 (1.31-18.40)
      Amp(1q21)
13/74 (17.6)
4/76 (5.3)
3.84 (1.19-12.38)
      Gain(1q21) or amp(1q21)
27/127 (21.3)
7/120 (5.8)
4.36 (1.82-10.44)
      1 HRCA
31/137 (22.6)
7/137 (5.1)
5.43 (2.30-12.83)
      ≥2 HRCAs
1/19 (5.3)
0/15 (0)
NE (NE-NE)
      Isolated gain(1q21)
14/47 (29.8)
3/42 (7.1)
5.52 (1.46-20.86)
      Isolated amp(1q21)
12/61 (19.7)
4/65 (6.2)
3.73 (1.13-12.31)
      Isolated gain(1q21) or amp(1q21)
26/108 (24.1)
7/107 (6.5)
4.53 (1.87-10.97)
      Gain(1q21) or amp(1q21) plus ≥1 HRCA
1/19 (5.3)
0/13 (0)
NE (NE-NE)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; Rd, lenalidomide + dexamethasone.
aOR >1 indicates an advantage for D-Rd.

Safety

  • Summary of grade 3/4 TEAEs among patients aged ≥75 years have been reported by Moreau et al (2025)7.

DARZALEX in Combination with Bortezomib, Melphalan, and Prednisone in Patients with NDMM

ALCYONE (MMY3007; NCT02195479) is a phase 3, multicenter, randomized, open-label, active-controlled study which evaluated the safety and efficacy of D-VMP compared with VMP alone for the treatment of NDMM in patients (N=706) who were ineligible for high-dose chemotherapy with ASCT.8 Mateos et al (2025)9 reported the final efficacy and safety results study at a median follow-up of 86.7 months.

Study Design/Methods

  • Primary endpoint: PFS
  • Secondary endpoints: MRD-negativity rate, time to subsequent antimyeloma therapy, PFS on next line of therapy, OS, safety, and European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-Core 30-item (C30) assessment

Results

Efficacy
  • The MRD-negativity rates (at 10-5 and 10-6 sensitivity level) were higher in the D-VMP group than in the VMP group. The D-VMP group had higher durable MRD-negativity rates (10-5 sensitivity level) for ≥6 months and ≥12 months compared with the VMP group. The MRD status of the D-VMP and VMP groups is summarized in Table: Summary of MRD-Negativity Rates and Durable MRD-Negativity Rates.9
  • In the D-VMP and VMP groups, longer OS was observed in patients who had MRD-negativity (HR, 0.60; 95% CI, 0.31-1.14) compared with those who did not have MRD-negativity (HR, 0.77; 95% CI, 0.62-0.95).9

Summary of MRD-Negativity Rates and Durable MRD-Negativity Rates9
Parameter
D-VMP
(n=350)
VMP
(n=356)
OR (95% CI)a,b
P Valuec
MRD-negativity, n (%)
   10-5
99 (28)
25 (7)
5.23 (3.27-8.36)
<0.0001
   10-6
33 (9)
3 (1)
12.96 (3.85-43.57)
<0.0001
Durable MRD-negativity (10-5)d, n (%)
   ≥6 months
56 (16)
16 (4)
4.05 (2.27-7.21)
<0.0001
   ≥12 months
49 (14)
10 (3)
5.63 (2.80-11.31)
<0.0001
Abbreviations: CI, confidence interval; D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ISS, International Staging System; MRD, minimal residual disease; OR, odds ratio; VMP, bortezomib + melphalan + prednisone.
Data are for the intent-to-treat population.
aMantel-Haenszel estimate of the common OR for stratified tables was used for MRD status. The stratification factors were ISS disease stage (I, II, or III), region (Europe vs other), and age (<75 years vs ≥75 years) as randomized. An OR >1 indicates an advantage for D-VMP.
bA Mantel-Haenszel estimate of the common OR without stratification was used for durable MRD status.
An OR >1 indicates an advantage for D-VMP.
cP values were derived from Fisher’s exact test.
dDurable MRD-negativity was defined as the absence of MRD confirmed at least 6 months or at least 12 months apart without any instances of MRD-positivity in between assessments.

Predictive and Prognostic Role of MRD-Negativity and Durability in ALCYONE Study

San-Miguel et al (2022)10 evaluated the predictive and prognostic role of MRD-negativity and durability in patients with NDMM ineligible for transplant in the ALCYONE study.

Results

Patient Characteristics


Demographics and Baseline Characteristics by MRD Durability (ALCYONE)50
Characteristic
D-VMP
VMP
ITT
(n=350)
MRD-Negative Patients
ITT
(n=356)
MRD-Negative Patients
At Any Time
(n=94)
≥12 Months
(n=49)
Not ≥12 Months
(n=45)
At Any Time
(n=25)
≥12 Months
(n=10)
Not ≥12 Months
(n=15)
Age, years
   Median
   (range)
71
(40-93)
71
(40-93)
71
(40-87)
71
(56-93)
71
(50-91)
73
(52-82)
72
(52-82)
74
(67-82)
Distribution
   <75
246 (70.3)
68 (72.3)
36 (73.5)
32 (71.1)
249 (69.9)
15 (60)
6 (60)
9 (60)
   ≥75
104 (29.7)
26 (27.7)
13 (26.5)
13 (28.9)
107 (30.1)
10 (40)
4 (40)
6 (40)
ISS disease stagea
   I
69 (19.7)
16 (17)
9 (18.4)
7 (15.6)
67 (18.8)
5 (20)
2 (20)
3 (20)
   II
139 (39.7)
39 (41.5)
23 (46.9)
16 (35.6)
160 (44.9)
10 (40)
5 (50)
5 (33.3)
   III
142 (40.6)
39 (41.5)
17 (34.7)
22 (48.9)
129 (36.2)
10 (40)
3 (30)
7 (46.7)
Cytogenetic profileb
   Patients
   evaluated
314
88
46
42
302
23
9
14
   Standard-risk
   cytogenetic
   abnormality
261 (83.1)
74 (84.1)
40 (87)
34 (81)
257 (85.1)
19 (82.6)
7 (77.8)
12 (85.7)
   High-risk
   cytogenetic
   abnormalityc
53 (16.9)
14 (15.9)
6 (13)
8 (19)
45 (14.9)
4 (17.4)
2 (22.2)
2 (14.3)
      del(17p)
29 (9.2)
8 (9.1)
4 (8.7)
4 (9.5)
27 (8.9)
3 (13)
1 (11.1)
2 (14.3)
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ISS, International Staging System; ITT, intention-to-treat; MRD, minimal residual disease; VMP, bortezomib + melphalan + prednisone.
All data are n (%) unless otherwise indicated.
aISS staging is derived based on the combination of serum β2-microglobulin and albumin.
bCytogenetic risk status was determined by fluorescence in situ hybridization or karyotype testing.
cHigh risk is defined as having a positive test for any of the del17p, t(14;16), or t(4;14) molecular abnormalities.

Efficacy

  • In the ITT population and among patients with ≥CR, patients receiving the D-VMP regimen achieved higher rates of MRD-negativity and durability compared with VMP. Please see Table: Rates of Sustained MRD-Negativity Status in Transplant-ineligible NDMM (ALCYONE).
  • In the ITT population, MRD-negative patients had improved PFS compared with MRD-positive patients.
  • Durable MRD-negativity lasting ≥6 months or ≥12 months improved PFS compared with MRD-negative patients who did not maintain MRD-negativity for ≥6 months or ≥12 months.
  • Estimated 36-month rates of time to subsequent anticancer therapy were mostly higher for patients who achieved MRD-negativity at any time vs MRD-positive patients, and for patients with sustained MRD-negativity lasting ≥6 months or ≥12 months compared with those who did not have durable MRD-negativity. Please see Table: Estimated Rates of Patients Without Subsequent Therapy at 36 Months in the ITT Population (ALCYONE).
  • Estimated 36-month PFS2 rate (ITT; D-VMP, n=350; VMP, n=356)50 :
    • MRD-negative (10-5 sensitivity) at ≥1 time point: D-VMP, 87% (n=94); VMP, 92% (n=25)
    • MRD-positive: D-VMP, 67.9% (n=256); VMP, 51.9% (n=331)

Rates of Sustained MRD-Negativity Status in Transplant-ineligible NDMM (ALCYONE)10
MRD-Negativity (10-5 Sensitivity)
(N=706)
D-VMP
VMP
P Valuea
ITT, n
350
356
   MRD-negative status, n (%)
94 (26.9)
25 (7)
<0.0001
      ≥6 months sustained
55 (15.7)
16 (4.5)
<0.0001
      ≥12 months sustained
49 (14)
10 (2.8)
<0.0001
≥CR
160
90
   MRD-negative status, n (%)
94 (58.8)
25 (27.8)
<0.0001
      ≥6 months sustained
55 (34.4)
16 (17.8)
0.0055
      ≥12 months sustained
49 (30.6)
10 (11.1)
0.0006
Abbreviations: CR, complete response; D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ITT, intention-to-treat; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; VMP, bortezomib + melphalan + prednisone.
aP value was calculated using Fisher’s exact test.

Estimated Rates of Patients Without Subsequent Therapy at 36 Months in the ITT Population (ALCYONE)10
Estimated 36-Month Time to Subsequent Anticancer Therapy Rate, n (%)
D-VMP
(n=350)
VMP
(n=356)
MRD-negative (10-5 sensitivity) at ≥1 time point
94 (88.7)
25 (75.3)
MRD-positive
256 (54.9)
331 (33.2)
Achieved and remained MRD-negative (10-5 sensitivity) for ≥6 months
55 (96.3)
16 (93.8)
MRD-negativity not ≥6 months
39 (77.2)
9 (38.9)
Achieved and remained MRD-negative (10-5 sensitivity) for ≥12 months
49 (95.8)
10 (100)
MRD-negativity not ≥12 months
45 (80.5)
15 (57.8)
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ITT, intention-to-treat; MRD, minimal residual disease; VMP, bortezomib + melphalan + prednisone.

DARZALEX in Combination with Bortezomib, Lenalidomide, and Dexamethasone in Patients with NDMM

GRIFFIN (MMY2004; NCT02874742) is an ongoing, 2-part, randomized, active-controlled, phase 2 US study evaluating the safety and efficacy of DARZALEX in combination with VRd in patients with NDMM eligible for HDT and ASCT.11 Voorhees et al (2021)12 reported the final analysis of the safety run-in cohort (part 1) of the GRIFFIN study. Voorhees et al (2020)11 reported the primary analysis and updated analysis of the randomized portion (part 2) of this study. Laubach et al (2021)51 presented updated efficacy and safety results after 2 years of maintenance therapy in this study. Sborov et al (2022)52 presented the final efficacy and safety results after all patients completed ≥1 year of follow-up after the end of study treatment.

Study Design/Methods

  • Primary endpoints: sCR (by end of post-ASCT consolidation)
  • Secondary endpoints: MRD (10-5 sensitivity via NGS), CR, ORR, ≥VGPR

Part 1: Safety Run-in Phase Final Analysis

Voorhees et al (2021)12 reported the final analysis of the safety run-in cohort (N=16) of the GRIFFIN study.  

Results

Efficacy

  • 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.
  • 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 sensitivity was sustained for ≥12 months in 8 (50%) patients.

Part 2: Final Efficacy and Safety Analysis of Maintenance Therapy

Voorhees et al (2023)13 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

Efficacy


Final Analysis of MRD-Negativity Rates at the End of Maintenance13,53
Parameter
D-VRd
VRd
P Value
MRD-negative
   ITT population, n
104
103
-
      10-5 sensitivity, n (%)
67 (64)
31 (30)
<0.0001a
         OR (95% CI)
4.23 (2.35-7.62)
      10-6 sensitivity, n (%)
37 (36)
16 (16)
0.0013a
         OR (95% CI)
2.95 (1.52-5.75)
   In patients achieving ≥CR, n
83
59
-
      10-5 sensitivity, n (%)
64 (77)
28 (47)
0.0004a
      10-6 sensitivity, n (%)
35 (42)
14 (24)
0.031a
Durable MRD-negativity
   Lasting ≥12 months, n
104
103
-
      10-5 sensitivity, n (%)
46 (44)
14 (14)
<0.0001a
         OR (95% CI)
5 (2.5-9.99)
      10-6 sensitivity, n (%)
10 (10)
4 (4)
0.16a
         OR (95% CI)
2.48 (0.76-8.07)
Abbreviations: CI, confidence interval; ≥CR, complete response or better; D-VRd, DARZALEX + bortezomib + lenalidomide + dexamethasone; ITT, intent-to-treat; MRD, minimal residual disease; OR, odds ratio; VRd, bortezomib + lenalidomide + dexamethasone.
aP value was calculated using the Fisher’s exact test.
Note: The predefined per protocol final analysis was performed 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.
  • 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 sensitivity). The 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,13,53
Timepoint, %
D-VRd
VRd
MRD-Negativity (10-5 Sensitivity)
MRD-Negativity (10-6 Sensitivity)
MRD-Negativity (10-5 Sensitivity)
MRD-Negativity (10-6 Sensitivity)
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, intent-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 were performed at the first evidence of suspected CR or sCR after induction (but before stem cell collection), consolidation, and 12 and 24 months of maintenance, regardless of response.
  • No patient in either treatment arm with sustained MRD-negativity 10-5 sensitivity lasting ≥12 months became MRD-Positive later.
  • The median time to MRD-negativity in the D-VRd vs VRd arm at the 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).

DARZALEX in Combination with Lenalidomide and Dexamethasone in Patients with RRMM

POLLUX (MMY3003; NCT02076009) is a phase 3, randomized, open-label, active-controlled, multicenter study that evaluated the safety and efficacy of Rd and D-Rd in patients with RRMM (N=569).15 Kaufman et al (2019)54 presented the updated safety and efficacy of the POLLUX study after a median follow-up of 54.8 months. Dimopoulos et al (2023)15 reported the updated efficacy and safety results of the POLLUX study at a median follow-up of 79.7 months. Results of this update are summarized below.

Study Design/Methods

  • Primary endpoint: PFS
  • Key secondary endpoints: ORR, ≥VGPR, ≥CR, OS, TTR, and MRD-negativity

Results

Patient Characteristics

  • Overall, 569 patients were included (D-Rd, n=286; Rd, n=283).
  • The median duration of follow-up was 79.7 (range, 0-86.5) months.

Efficacy

  • In the D-Rd vs Rd arm, the MRD-negativity rate (10-5 sensitivity) was 33.2% vs 6.7% (P<0.0001). MRD-negativity was associated with improved OS in both the treatment arms.

Safety

  • No new safety signals were identified with the updated follow-up. Most common (>15% of patients) and grade 3/4 (>5% of patients) TEAEs in the safety population of the POLLUX study have been reported by Dimopoulos et al (2023).15

DARZALEX in Combination with Bortezomib and Dexamethasone in Patients with RRMM

CASTOR (MMY3004; NCT02136134) is an open-label, randomized, multicenter, active-controlled, phase 3 study which evaluated the safety and efficacy of Vd alone compared to D-Vd in patients with RRMM (N=498). Sonneveld et al (2022)17 reported updated results of the CASTOR study, including OS, at a median follow-up of 72.6 months. Results of this update are summarized below.

Study Design/Methods

  • Primary endpoint: PFS
  • Secondary endpoints: time to disease progression, overall response, DOR, TTR, ≥VGPR, OS, and MRD

Results

Efficacy

  • The median duration of follow-up was 72.6 (range, 0-79.8) months.
  • MRD-negativity rate at a 10-5 sensitivity threshold was 15.1% with D-Vd vs 1.6% with Vd (P <0.0001).

Safety

  • Updated most common (>15% of patients) and grade 3/4 TEAEs (>5% of patients) in the safety population of the CASTOR study have been reported by Sonneveld et al (2022).17

DARZALEX in Combination with Carfilzomib and Dexamethasone in Patients with RRMM

CANDOR (NCT03158688) is a randomized, open-label, multicenter, phase 3 study evaluating the efficacy and safety of D-Kd vs Kd in patients with RRMM. Usmani et al (2023)19 reported the final efficacy and safety results of the CANDOR study after a median follow-up of approximately 50 months.

Study Design/Methods

  • Primary endpoint: PFS
  • Key secondary endpoints: ORR, MRD (10-5 sensitivity), and OS

Results

Efficacy


Overall Survival and MRD-Negativity (10-5 Sensitivity) Rates (CANDOR)19
Parameter
D-Kd, % (95% CI)
(n=312)
Kd, % (95% CI)
(n=154)
MRD-negativity rate at 12 months
n=57
n=8
18.3 (14.1-23)
5.2 (2.3-10)
   OR (95% CI)
4.403 (2.007-9.656)
MRD-negative CR rate at 12 months
n=40
n=3
12.8 (9.3-17)
1.9 (0.4-5.6)
   OR (95% CI)
7.819 (2.364-25.858)
MRD-negativity rate at any time
n=87
n=14
27.9 (23-33.2)
9.1 (5.1-14.8)
   OR (95% CI)
4.222 (2.277-7.829)
MRD-negative CR rate at any time
n=68
n=12
21.8 (17.3-26.8)
7.8 (4.1-13.2)
   OR (95% CI)
3.551 (1.833-6.877)
Abbreviations: CI, confidence interval; CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; HR, hazard ratio; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; OR, odds ratio.

Safety

  • TEAEs in the safety population of the CANDOR study have been reported by Usmani et al (2023).19

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 R in VRd group in patients with NDMM eligible for ASCT. Sonneveld et al (2023)20 reported efficacy and safety results from the PERSEUS study evaluating D-VRd vs VRd in patients with NDMM eligible for ASCT.

Study Design/Methods

  • A total of 709 patients were randomized 1:1 to into D-VRd (n=355) vs VRd (n=354) arm.
    • Stratification was done based on the ISS disease stage (I, II, or III) and standard or high cytogenetic risk (defined as the absence or presence, respectively, of a del[17p], t[4;14], or t[14;16]).
  • Dosing:
    • Induction and consolidation: Total duration of induction and consolidation treatment was 6 cycles. Each cycle was 28 days.
      • D-VRd:
        • DARZALEX FASPRO- 1800 mg once every week (QW) at cycles 1-2 and once every 2 weeks (Q2W) at cycles 3-4
        • SC bortezomib- 1.3 mg/m2 on days 1, 4, 8, and 11 of each cycle
        • Orally (PO)/IV lenalidomide- 25 mg on days 1-21 of each cycle
        • PO/IV dexamethasone- 40 mg on days 1-4 and days 9-12 of each cycle
      • VRd:
        • SC bortezomib- 1.3 mg/m2 on days 1, 4, 8, and 11 of each cycle
        • PO lenalidomide- 25 mg daily on days 1-21 of each cycle
        • PO/IV dexamethasone- 40 mg on days 1-4 and days 9-12 of each cycle
    • Maintenance: Total duration of maintenance (≥24 months) was cycle 7 until PD. Each cycle was 28 days.
      • D-VRd:
        • DARZALEX FASPRO- 1800 mg SC once every 4 weeks (Q4W)
        • PO lenalidomide- 10 mg until PD or unacceptable toxicity
        • Patients who achieved sustained MRD for 12 months after ≥24 months of maintenance discontinued DARZALEX FASPRO, but continued PO lenalidomide until PD or unacceptable toxicity. Once they experienced loss of MRD-negativity or CR, they restarted on DARZALEX FASPRO.
        • Patients who did not achieve sustained MRD for 12 months after ≥24 months of maintenance continued DARZALEX FASPRO and PO lenalidomide
      • VRd:
        • PO lenalidomide-10 mg daily until PD or unacceptable toxicity
  • Primary endpoint: PFS.
  • Key secondary endpoints: Overall ≥CR, overall MRD-negativity, and OS.
  • Other secondary endpoints: ORR, ≥VGPR, sCR, duration of MRD-negativity.

Results

Patient Characteristics

  • A total of 709 patients were randomized into the D-VRd (n=355) and VRd (n=354) groups.
  • 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 group, who started the induction phase continued into the maintenance phase, respectively.
    • A total of 207/322 patients in the D-VRd group 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 group received ASCT, respectively.
  • The median duration of follow-up was 47.5 months (range, 0-54.4).

Efficacy

  • A summary of response rates and MRD status in the ITT population is presented in Table: Summary of MRD Status in the ITT Population.
  • Analyses of overall ≥CR rates and overall MRD-negativity rates (at 10-5 sensitivity) in prespecified subgroups appeared to favor D-VRd over VRd across clinically relevant subgroups.

Summary of MRD Status in the ITT Populationa,20
Parameter
D-VRd (n=355)
VRd (n=354)
P Valueb
MRD-negativityc, 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 sensitivity) for ≥12 months, n (%)
230 (64.8)
105 (29.7)
-
Abbreviations: CR, complete response; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; IMWG, International Myeloma Working Group; ITT, intention-to-treat; MRD, minimal residual disease; NGS, next-generation sequencing; 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.
CThe 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.

Safety

  • Most common AEs during treatment in the safety population of the PERSEUS study have been reported by Sonneveld et al (2023).20

Significance of CTC as a Biomarker in Transplant-Eligible NDMM Patients - Results From the PERSEUS Study

Bertamini et al (2024)21 presented results from the PERSEUS study that highlighted the significance of CTC as a biomarker in transplant-eligible NDMM patients.

Results

Patient Characteristics


Baseline Characteristics in Patients From the PERSEUS Study - CTC Subgroup21
Characteristic
D-VRd
(n=231)
VRd
(n=220)
P Value
CTC detected, n/N (%)
183/231 (79.2)
187/220 (85)
0.73
CTC, median (IQR), %
0.0104 (0.0009-0.0738)
0.0088 (0.0012-0.0746)
0.88
Median age (IQR), years
60 (53.5-65)
59 (52.8-65)
0.71
Female sex, n (%)
84 (36.4)
95 (43.2)
0.14
ISS disease stage, %
   I
53.2
50.9
0.76
   II
31.6
35
0.76
   III
15.2
14.1
0.76
High LDH, n (%)
63 (27.3)
42 (19.1)
0.04
Cytogenetic high-riska, n (%)
51 (22.1)
49 (22.3)
0.86
Abbreviations: CTC, circulating tumor cell; D-VRd, DARZALEX FASPRO + bortezomib, lenalidomide, and dexamethasone; IQR, interquartile range; ISS, International Staging System; LDH, lactate dehydrogenase; VRd, bortezomib, lenalidomide, and dexamethasone.aHigh-risk cytogenetics was defined by the presence of t(4;14) and/or t(14;16) and/or del17p by fluorescence in situ hybridization.

Efficacy

  • D-VRd vs VRd significantly improved patient outcomes across both high and low CTC levels (P<0.0001).21
    • D-VRd vs VRd improved MRD-negativity rates (with ≥CR; 10-5 and 10-6 sensitivities) and sustained MRD-negativity rates (with ≥CR; 10-5 and 10-6 sensitivities; ≥12 months) in patients with both high and low CTC levels, and the results are presented in Table: Summary of Overall MRD-Negativity (With ≥CR) Rates.21

Summary of Overall MRD-Negativity (With ≥CR) Rates21
Patients, %
CTC Low Levela
CTC High Levelb
D-VRd
(n=195)
VRd
(n=187)
P Value
D-VRd
(n=36)
VRd
(n=33)
P Value
Overall MRD-negativity (with ≥CR)c
   10-5 sensitivity
74
58
<0.001d
69
33
<0.01d
   10-6 sensitivity
66
39
<0.001d
47
21
<0.01d
Sustained MRD-negativity (with ≥CR; ≥12 months)e
   10-5 sensitivity
64
36
<0.0001f
50
15
<0.01f
   10-6 sensitivity
42
21
<0.0001f
39
6
<0.01f
Abbreviations: CI, confidence interval; CR, complete response; CTC, circulating tumor cell; D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; ITT, intention-to-treat; MRD, minimal residual disease; NGS, next-generation sequencing; VRd, bortezomib + lenalidomide + dexamethasone.
aCTC-low is defined by CTC <0.175%.
bCTC-high is defined by CTC ≥0.175%.
cProportion of patients who achieved both MRD-negativity and ≥CR in the randomized ITT population.dP value from a Chi-square test.eTwo consecutive MRD-negative results ≥12 months apart with no MRD-positive results in between.fP value from a Fisher’s test.

DARZALEX FASPRO in Combination with Pomalidomide and Dexamethasone in Patients with RRMM

APOLLO (MMY3013; NCT03180736) is an ongoing phase 3, randomized, open-label, multicenter study evaluating the safety and efficacy of D-Pd vs Pd in patients with RRMM who received ≥1 prior treatment with both lenalidomide and a PI. Dimopoulos et al (2021)22 reported the primary analysis of this study.

Study Design/Methods

  • Primary endpoint: PFS
  • Key secondary endpoints: ORR, MRD-negativity rate (10-5 sensitivity via NGS), ≥VGPR, ≥CR, and OS

Results

Patient Characteristics

  • The ITT population consisted of 151 patients in the D-Pd arm and 153 patients in the Pd arm.

Efficacy

  • After a median follow-up of 16.9 months, MRD-negativity rate was 9% in patients treated with D-Pd vs 2% with Pd (OR, 4.7; 95% CI, 1.3-16.9; P=0.010).

Safety

  • Most common AEs in the safety population of the APOLLO study has been reported by Dimopoulos et al (2021).22

DARZALEX FASPRO in Combination with 4 Standard-of-Care Regimens

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)23 presented the results of safety and efficacy analysis of D-VRd, D-VMP, and D-Rd in the PLEIADES study. Moreau et al (2020)24 presented updated safety and efficacy results of the D-Kd, D-Rd, and D-VMP arms in the PLEIADES study.

Study Design/Methods  

  • D-VRd for patients with transplant-eligible NDMM (n=67).
  • D-VMP for patients with transplant-ineligible NDMM (n=67).
  • D-Rd for patients with RRMM with ≥1 LOT (n=65)
  • D-Kd in patients with RRMM with 1PL (n=60)
  • Primary endpoints: ORR for the D-VMP and D-Rd cohorts; ≥VGPR after the 4 induction cycles for the D-VRd cohort
  • Key secondary endpoints: ≥CR, DOR, MRD-negativity rate and ≥VGPR for the D-VMP, D-Rd cohorts; ORR for the D-VRd cohort

Results - D-VRd, D-VMP, and D-Rd

Efficacy

  • The pre-specified primary analysis with a median follow-up was 3.9 months, 6.9 months, and 7.1 months for D-VRd, D-VMP, and D-Rd cohorts, respectively.
  • At a subsequent clinical cut-off, the median duration of follow-up was 14.3 months, and 14.7 months for D-VMP, and D-Rd cohorts respectively.
  • Primary endpoints were met for all 3 cohorts and response rates were similar to DARZALEX studies in GRIFFIN11, ALCYONE8, and POLLUX14.
  • MRD-negativity rates were evaluated via NGS at a sensitivity threshold of 10-5.
    • MRD-negativity rates were 16.4% (90% CI, 9.4-25.7) in the D-VMP cohort and 15.4% (90% CI, 8.6-24.7) in the D-Rd cohort.

Safety

  • Safety summary in the D-VRd, D-VMP, and D-Rd cohorts, and most common grade 3/4 TEAEs (≥5% in any cohorts) of the PLEIADES study have been reported by Chari et al (2021).23

Moreau et al (2020)24 presented updated safety and efficacy results of the D-Kd, D-Rd, and D-VMP arms in the PLEIADES study.

Results - D-Kd, D-Rd, and D-VMP

Efficacy

  • Median duration of follow-up was 9.2 months (primary analysis), 25.7 months, and 25.2 months for D-Kd, D-Rd, and D-VMP cohorts, respectively.
  • Response rates were similar to DARZALEX studies in CANDOR18, POLLUX54, and ALCYONE55
  • MRD-negativity rates were evaluated via NGS at a sensitivity threshold of 10-5.
    • MRD-negativity rates were 24.2% in the D-Kd cohort, 20% in the D-Rd cohort, and 25.4% in the D-VMP cohort.
    • MRD-negative ≥CR rates were 21.2% in the D-Kd cohort, 20% in the D-Rd cohort, and 25.4% in the D-VMP cohort.

Safety

  • Summary of TEAEs occurring in the D-Kd, D-Rd, and D-VMP cohorts of the PLEIADES study have been reported by Moreau et al (2020).24

DARZALEX FASPRO in Combination with Lenalidomide

AURIGA (MMY3021; NCT03901963) is an ongoing, open-label, active-controlled, multicenter, randomized, phase 3 study evaluating the conversion rate to MRD-negativity after maintenance treatment with D-R vs lenalidomide alone in patients with NDMM who are MRD-positive after ASCT.25-27

Badros et al (2024)25,26 reported primary results from the phase 3 AURIGA study.

Study Design/Methods

  • The trial enrolled 200 patients from the United States and Canada.25
  • Patients underwent 1:1 randomization to receive D-R (n=99) or R alone (n=101) across 28-day cycles.25,27
    • D-R: DARZALEX FASPRO 1800 mg SC QW in cycles 1-2, Q2W in cycles 3-6, Q4W in cycles 7+.
    • R: Lenalidomide 10 mg PO once a dayon days 1-28.
  • The treatment regimen continued until unacceptable toxicity, disease progression, consent withdrawal, or for a maximum of 36 cycles.25
  • Primary endpoint: MRD-negativity conversion rate from baseline by 12 months.25
    • MRD was assessed at 12, 18, 24, and 36 months.
    • If lenalidomide is well tolerated, the dose may be increased to 15 mg daily after cycle 3, at the investigator’s discretion.
  • Secondary endpoints: Safety, PFS, overall MRD-negativity conversion rate, sustained MRD-negativity rate (≥6 months), response rates including CR/sCR as assessed by International Myeloma Working Group 2016 criteria, duration of ≥CR, OS, HRQoL changes based on patient reported outcomes.25

Results

Patient Characteristics

  • A total of 200 patients were randomized into the D-R maintenance (n=99) and R alone maintenance (n=101) arms.25
  • The median duration of treatment was 30.7 (range, 0.7-37.5) months vs 20.6
    (range, 0-37.7) months in the D-R vs R arm, respectively.25
  • The baseline demographics and disease characteristics of the ITT population are presented in Table: Baseline Demographics and Disease Characteristics of the ITT Population.25
  • The median follow-up was 32.3 months.25
  • Patients in the D-R vs R arm received a median of 33 (range, 1-36) vs 21.5
    (range, 1-36) maintenance cycles, respectively.25
  • Overall, 85 of 96 (88.5%) vs 77 of 98 (78.6%) patients in the D-R vs R arm completed ≥12 maintenance cycles, respectively.25

Baseline Demographics and Disease Characteristics of the ITT Population25
D-R (n=99)
R (n=101)
Median age (range), years
63 (35-77)
62 (35-78)
   <65 years, n (%)
61 (61.6)
61 (60.4)
   65-70 years, n (%)
23 (23.2)
21 (20.8)
   ≥70 years, n (%)
15 (15.2)
19 (18.8)
Sex, n (%)
   Male
61 (61.6)
58 (57.4)
   Female
38 (38.4)
43 (42.6)
Race, n (%)
   White
67 (67.7)
68 (67.3)
   Black or African American
20 (20.2)
24 (23.8)
   Asian
5 (5.1)
1 (1)
   American Indian or Alaska Native
0 (0)
1 (1)
   Othera
5 (5.1)
5 (5)
   NR
2 (2)
2 (2)
ECOG PS, n (%)
   0
45 (45.5)
55 (54.5)
   1
52 (52.5)
44 (43.6)
   2
2 (2)
2 (2)
ISS disease stageb, n (%)
   I
40 (44)
38 (38.8)
   II
28 (30.8)
37 (37.8)
   III
23 (25.3)
23 (23.5)
Median induction cycles (range)c, n
5 (4-8)
5 (4-8)
Cytogenetic risk at diagnosisd, n (%)
   Standard risk
63 (68.5)
66 (74.2)
   High riske
22 (23.9)
15 (16.9)
      del(17p)
13 (14.1)
3 (3.4)
      t(4;14)
10 (10.9)
12 (13.5)
      t(14;16)
6 (6.5)
7 (7.9)
   Unknown
7 (7.6)
8 (9)
Revised cytogenetic risk at diagnosisf, n (%)
   Standard risk
52 (55.9)
53 (59.6)
   High riskg
32 (34.4)
30 (33.7)
      del(17p)
13 (14)
3 (3.4)
      t(4;14)
10 (10.8)
12 (13.5)
      t(14;16)
6 (6.5)
7 (7.9)
      t(14;20)
1 (1.1)
2 (2.2)
      gain/amp(1q21)
16 (17.2)
22 (24.7)
   Unknown
9 (9.7)
6 (6.7)
Abbreviations: D-R, DARZALEX FASPRO+lenalidomide; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; ITT, intention-to-treat; NR, not reported; R, lenalidomide.
aPatients reporting multiple races.
bD-R vs R: n=91 vs n=98, respectively.
cD-R vs R: n=98 vs n=99, respectively.
dD-R vs R: n=92 vs n=89, respectively.
eHigh risk is defined as positive for any of del(17p), t(14;16), or t(4;14).
fD-R vs R: n=93 vs n=89, respectively.
gRevised high-risk cytogenetics is defined as ≥1 abnormality from del(17p), t(4;14), t(14;16), t(14;20), and gain/amp(1q21).

Efficacy

  • The MRD status in the ITT population are summarized in Table: Summary of MRD Status in the ITT Population.25,26
    • The MRD-negativity (10-5 sensitivity) conversion rate by 12 months from initiation of maintenance (primary endpoint), was significantly higher for D-R vs R (50.5% vs 18.8%; OR, 4.51; 95% CI, 2.37-8.57; P<0.0001).
    • The D-R arm yielded ~2.5 times greater sustained MRD-negativity (10-5 sensitivity) rates at ≥6 months (35.4% vs 13.9%) and relatively higher sustained MRD-negativity (10-5 sensitivity) rates at ≥12 months (17.2% vs 5%) than the R arm.
  • Subgroup analyses of MRD-negativity (10-5 sensitivity) conversion rates at 12 months appeared to consistently favor D-R over R across most clinically relevant subgroups, including patients with a standard or high cytogenetic risk and older patients; the results are summarized in Table: Subgroup Analysis of MRD-Negativity (10-5) Conversion Rate From Baseline to 12 Months of Maintenance Treatment in the ITT Population.25

Summary of MRD Status in the ITT Population25,26
Parameter
D-R (n=99)
R (n=101)
ORa (95% CI)
P-Valueb
Overall MRD-negativity conversion ratec, n (%)
   10-5 sensitivity
60 (60.6)
28 (27.7)
4.12 (2.26-7.52)
<0.0001
   10-6 sensitivity
36 (36.4)
13 (12.9)
3.91 (1.91-7.99)
0.0001
MRD-negativity conversion rate at 12 months from start of maintenance, n (%)
   10-5 sensitivity
50 (50.5)
19 (18.8)
4.51 (2.37-8.57)
<0.0001
   10-6 sensitivity
23 (23.2)
5 (5)
5.97 (2.15-16.58)
0.0002
Sustained MRD-negativity (10-5), n (%)
   ≥6 monthsd
35 (35.4)
14 (13.9)
3.40 (1.69-6.83)
0.0005
   ≥12 monthsd
17 (17.2)
5 (5)
4.08 (1.43-11.62)
0.0065
Abbreviations: CI, confidence interval; D-R, DARZALEX FASPRO + lenalidomide; ITT, intention-to-treat; MRD, minimal residual disease; OR, odds ratio; R, lenalidomide.aMantel-Haenszel estimate of the common OR for stratified tables was used. The stratification factor was the baseline cytogenetic risk per investigator assessment (high vs standard/unknown) as used for randomization. An OR of >1 indicates an advantage for the D-R arm.
bAll parameters, except ≥CR were assessed using Fisher’s exact test.
cAt a median follow-up of 32.3 months.dSustained MRD-negativity at ≥6 months and ≥12 months is defined as an MRD-negative status (at 10-5 sensitivity threshold) in 2 bone marrow aspirate assessments spaced a minimum of 6 months and 12 months apart, respectively, without any assessment showing an MRD-positive status in between the assessments.

Subgroup Analysis of MRD-Negativity (10-5) Conversion Rate From Baseline to 12 Months of Maintenance Treatment in the ITT Population25
Subgroup, n/N (%)
D-R (n=99)
R (n=101)
OR (95% CI)
ITT (overall)
50/99 (50.5)
19/101 (18.8)
4.51 (2.37-8.57)
Sex
   Male
32/61 (52.5)
11/58 (19)
4.71 (2.06-10.78)
   Female
18/38 (47.4)
8/43 (18.6)
3.94 (1.45-10.68)
Age
   <65 years
30/61 (49.2)
12/61 (19.7)
3.95 (1.76-8.85)
   ≥65 years
20/38 (52.6)
7/40 (17.5)
5.24 (1.86-14.74)
Race
   White
31/67 (46.3)
14/68 (20.6)
3.32 (1.55-7.10)
   Black
12/20 (60)
4/24 (16.7)
7.50 (1.85-30.34)
   Other
7/12 (58.3)
1/9 (11.1)
11.20 (1.04-120.36)
Weight
   ≤70 kg
12/23 (52.2)
4/18 (22.2)
3.82 (0.96-15.18)
   >70 kg
38/76 (50)
15/81 (18.5)
4.40 (2.14-9.03)
Baseline ECOG PS score
   0
20/45 (44.4)
9/55 (16.4)
4.09 (1.62-10.31)
   ≥1
30/54 (55.6)
10/46 (21.7)
4.50 (1.86-10.88)
ISS staging at diagnosis
   I
19/40 (47.5)
8/38 (21.1)
3.39 (1.25-9.19)
   II
13/28 (46.4)
7/37 (18.9)
3.71 (1.23-11.25)
   III
15/23 (65.2)
3/23 (13)
12.50 (2.83-55.25)
Cytogenetic risk at diagnosis
   High riska
7/22 (31.8)
1/15 (6.7)
6.53 (0.71-60.05)
   Standard risk
35/63 (55.6)
14/66 (21.2)
4.64 (2.15-10.04)
Revised cytogenetic risk at diagnosis
   High riskb
14/32 (43.8)
4/30 (13.3)
5.06 (1.43-17.88)
   Standard risk
28/52 (53.8)
12/53 (22.6)
3.99 (1.72-9.26)
Abbreviations: CI, confidence interval; D-R, DARZALEX FASPRO+lenalidomide; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; ITT, intention-to-treat; MRD, minimal residual disease; OR, odds ratio; R, lenalidomide.
aHigh risk is defined as positive for any of the following abnormalities: del(17p), t(14;16), or t(4;14).
bRevised high-risk cytogenetics is defined as ≥1 abnormality from del(17p), t(4;14), t(14;16), t(14;20), and gain/amp(1q21).

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).29-31 Usmani et al (2025)31 reported results from the phase 3 CEPHEUS study.

Study Design/Methods

  • The trial has enrolled 395 patients from 13 different countries including the United States.30 
  • Primary endpoint: Overall MRD-negativity (≥CR) rate at 10-5 sensitivity threshold.29,30
  • Key secondary endpoints: PFS, ORR, ≥VGPR, ≥CR, PFS2, OS, and sustained MRD-negativity (10-5) rate at ≥12 months.29,30

Results

Patient Characteristics


Baseline Demographics and Clinical Characteristics of the ITT Populationa,31
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)
Maleb, n (%)
87 (44.2)
111 (56.1)
Raceb, 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 PSc, n (%)
   0
71 (36)
84 (42.4)
   1
103 (52.3)
100 (50.5)
   2
23 (11.7)
14 (7.1)
Frailty scored, 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)
      Othere
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 stagef, n (%)
   I
68 (34.5)
68 (34.3)
   II
73 (37.1)
75 (37.9)
   III
56 (28.4)
55 (27.8)
Cytogenetic risk profileg, n (%)
   Standard risk
149 (75.6)
149 (75.3)
   High risk
25 (12.7)
27 (13.6)
   Indeterminateh
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

  • 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%).31
    • 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%).31
    • 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.

Summary of MRD Status and Response Rates in the ITT Population31
Parameter
D-VRd (n=197)
VRd (n=198)
OR (95% CI)
P Value
Overall MRD-negativitya, %
   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
Responseb, 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 Rates31
Subgroup
D-VRd
VRd
OR (95% CI)
Number of Patients With MRD-Negativity/
Total Number of Patients (%)
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.

Expanded Analysis of MRD Outcomes - Results From the CEPHEUS Study

Zweegman et al (2024)32 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.32

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 10-6 sensitivities) vs VRd alone at all prespecified timepoints.32
    • D-VRd almost doubled sustained MRD-negativity (≥) CR rates at 12, 24, and 36 months.32
    • Among patients who achieved both MRD-negativity (10-6 sensitivity) and ≥CR with D-VRd, >85% were alive and progression free at 54 months.32
  • D-VRd vs VRd showed PFS benefit regardless of the MRD-negativity status (10-6 sensitivity).32
    • 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 Analysis32
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 monthsb
49.2
27.3
2.56 (NR)
<0.0001
   ≥24 monthsc
42.1
22.7
2.47 (NR)
<0.0001
   ≥36 monthsd
29.9
15.2
2.37 (NR)
0.0005
Sustained MRD-negativity (10-6 sensitivity; ≥CR)a, %
≥12 monthsb
34
16.2
NR
NR
   ≥24 monthsc
27.9
13.6
NR
NR
   ≥36 monthsd
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 Subgroups32
Subgroups,
n/N (%)
D-VRd
VRd
OR
(95% CI)
D-VRd
VRd
OR
(95% CI)
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; 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.

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 03 June 2025. For purposes of streamlining, this scientific response has been limited to phase 2/3 clinical studies.

In response to your specific request, summarized in this response are the relevant data from company-sponsored studies pertaining to this topic.

 

References

Show
1 Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394:29-38.  
2 Moreau P, Hulin C, Perrot A, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(10):1378-1390.  
3 Moreau P, Hulin C, Perrot A, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial. Lancet Oncol. 2024;25(8):1003-1014.  
4 Corre J, Vincent L, Moreau P, et al. Daratumumab/bortezomib/thalidomide/dexamethasone in newly diagnosed myeloma: CASSIOPEIA minimal residual disease results. [Published online ahead of print March 24, 2025]. Blood. 2025. doi:10.1182/blood.2024027620.  
5 Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115.  
6 Facon T, Moreau P, Weisel K, et al. Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. Leukemia. 2025;39(4):942-950.  
7 Moreau P, Facon T, Usmani SZ, et al. Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study. Leukemia. 2025;39(3):710-719.  
8 Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518-528.  
9 Mateos MV, San-Miguel J, Cavo M, et al. Bortezomib, melphalan, and prednisone with or without daratumumab in transplant-ineligible patients with newly diagnosed multiple myeloma (ALCYONE): final analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2025;26(5):596-608.  
10 San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood. 2022;139(4):492-501.  
11 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.  
12 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.  
13 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.  
14 Dimopoulos M, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(14):1319-1331.  
15 Dimopoulos M, Oriol A, Nahi H, et al. Overall survival with daratumumab, lenalidomide, and dexamethasone in previously treated multiple myeloma (POLLUX): a randomized, open-label, phase III trial. J Clin Oncol. 2023;41(8):1590-1599.  
16 Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754-766.  
17 Sonneveld P, Chanan-Khan A, Weisel K, et al. Overall survival with daratumumab, bortezomib, and dexamethasone in previously treated multiple myeloma (CASTOR): a randomized, open-label, phase III trial. J Clin Oncol. 2023;41(8):1600-1609.  
18 Dimopoulos M, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396(10245):186-197.  
19 Usmani S, Quach H, Mateos M, et al. Supplement to: Final analysis of carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone in the CANDOR Study. Blood Adv. 2023;7(14):3739-3748.  
20 Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;390(4):301-313.  
21 Bertamini L, Fokkema C, Rodriguez-Otero P, et al. Circulating tumor cells as a biomarker to identify high-risk transplant-eligible myeloma patients treated with bortezomib, lenalidomide, and dexamethasone with or without daratumumab during induction/consolidation, and lenalidomide with or without daratumumab during maintenance: results from the PERSEUS study. Oral Presentation presented at: The 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2024; San Diego, CA.  
22 Dimopoulos M, Terpos E, Boccadoro M, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(6):801-812.  
23 Chari A, Rodriguez-Otero P, McCarthy H, et al. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label phase II study. Br J Haematol. 2021;192(5):869-878.  
24 Moreau P, Chari A, Haenel M, et al. Subcutaneous daratumumab (DARA SC) plus standard-of-care (SoC) regimens in multiple myeloma (MM) across lines of therapy in the phase 2 PLEIADES study: initial results of the DARA SC plus carfilzomib/dexamethasone (D-Kd) cohort, and updated results for the DARA SC plus bortezomib/melphalan/prednisone (D-VMP) and DARA SC plus lenalidomide/dexamethasone (D-Rd) cohorts. Poster presented at: The 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual.  
25 Badros A, Foster L, Anderson LD Jr, et al. Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study. Blood. 2025;145(3):300-310.  
26 Badros A, Foster L, Anderson LD Jr, et al. Subcutaneous daratumumab plus lenalidomide versus lenalidomide alone as maintenance therapy in newly diagnosed multiple myeloma after transplant: primary results from the phase 3 AURIGA study. Oral Presentation presented at: The 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
27 Janssen Research & Development, LLC. A study of daratumumab plus lenalidomide versus lenalidomide alone as maintenance treatment in participants with newly diagnosed multiple myeloma who are minimal residual disease positive after frontline autologous stem cell transplant (AURIGA). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 June 03]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03901963 NLM Identifier: NCT03901963.  
28 Badros A, Foster L, Anderson LD Jr, et al. Supplement to: Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study. Blood. 2025;145(3):300-310.  
29 Zweegman S, Usmani S, Chastian K, et al. Bortezomib, lenalidomide, and dexamethasone (VRd) ± daratumumab in patients with newly diagnosed multiple myeloma for whom transplant is not planned as initial therapy: a multicenter, randomized, phase 3 study (CEPHEUS). Poster presented at: The Annual Meeting of the American Society of Clinical Oncology (ASCO). May 31-June 4, 2019; Chicago, IL.  
30 Janssen Research & Development, LLC. A study comparing daratumumab, velcade (bortezomib), lenalidomide, and dexamethasone (D-VRd) with velcade, lenalidomide, and dexamethasone (VRd) in participants with untreated multiple myeloma and for whom hematopoietic stem cell transplant is not planned as initial therapy. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 June 03]. Available from: https://clinicaltrials.gov/ct2/show/NCT03652064 NML Identifier: NCT03652064.  
31 Usmani SZ, Facon T, Hungria V. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS study. doi.org/10.1038/s41591-024-03485-7. Nat Med. 2025.  
32 Zweegman S, Facon T, Hungria V, et al. Daratumumab + bortezomib, lenalidomide and dexamethasone (VRd) versus VRd alone in patients with newly diagnosed multiple myeloma ineligible for SCT or for whom SCT is not planned as initial therapy: analysis of minimal residual disease in the phase 3 CEPHEUS trial. Oral Presentation presented at: The 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2024; San Diego, CA.  
33 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.  
34 Moreau P, Facon T, Usmani S, et al. Daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): clinical assessment of key subgroups of the phase 3 MAIA study. Poster presented at: The German Society for Hematology and Medical Oncology (DGHO) Annual Conference; October 13-16, 2023; Hamburg, Germany.  
35 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.  
36 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;00:1-6.  
37 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).  
38 Spencer A, Moreau P, Mateos MV, et al. Daratumumab in combination with bortezomib plus dexamethasone (D-Vd) or lenalidomide plus dexamethasone (D-Rd) in relapsed or refractory multiple myeloma (RRMM): subgroup analysis of the phase 3 CASTOR and POLLUX studies in patients with early or late relapse after initial therapy. presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL/Virtual Meeting.  
39 Spencer A, Moreau P, Mateos MV, et al. Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX. Blood Adv. 2024;8(2):388-398.  
40 Spencer A, Moreau P, Mateos MV, et al. Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX. Blood Advances. 2024;8(2):388-398.  
41 Rodriguez-Otero P, Moreau P, Dimopoulos MA, et al. Daratumumab (DARA) + bortezomib/lenalidomide/dexamethasone (VRd) with DARA-R (D-R) maintenance in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM): analysis of minimal residual disease (MRD) in the PERSEUS trial. Oral Presentation presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2024; Chicago, IL, USA.  
42 Dimopoulos MA, Sonneveld P, Rodriguez-Otero P, et al. Daratumumab (DARA)/ bortezomib/lenalidomide/ dexamethasone (D-VRd) with D-R maintenance in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): analysis of PERSEUS based on cytogenetic risk. Poster presented at: The European Hematology Association (EHA) Hybrid Congress; June 13-16, 2024; Madrid, Spain.  
43 Dimopoulos MA, Sonneveld P, Rodriguez-Otero P, et al. Daratumumab (DARA SC)/bortezomib/lenalidomide/dexamethasone (D-VRd) with D-R maintenance in transplant-eligible (TE) newly diagnosed myeloma (NDMM): PERSEUS cytogenetic risk analysis. Oral Presentation presented at: 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
44 Rodriguez-Otero P, Voorhees PM, Boccadoro M, et al. Daratumumab plus bortezomib, lenalidomide, and dexamethasone in transplant-eligible patients with multiple myeloma: a pooled analysis of patients aged ≥65 years from both PERSEUS and GRIFFIN studies. Poster presented at: The 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.  
45 Foster L, Anderson LD Jr, Chung A, et al. Daratumumab plus lenalidomide (D-R) versus lenalidomide (R) alone as maintenance therapy in newly diagnosed multiple myeloma (NDMM) after transplant: analysis of the phase 3 AURIGA study among clinically relevant subgroups. Oral Presentation presented at: The 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2024; San Diego, CA.  
46 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. Clin Lymphoma Myeloma Leuk. 2025.  
47 Moreau P, Hulin C, Perrot A, et al. Supplement to: Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial. [published online ahead of print June 14, 2024]. Lancet Oncol. 2024. doi:10.1016/s1470-2045(24)00282-1.  
48 Corre J, Vincent L, Moreau P, et al. Supplement to: Daratumumab/bortezomib/thalidomide/dexamethasone in newly diagnosed myeloma: CASSIOPEIA minimal residual disease results. [Published online ahead of print March 24, 2025]. Blood. 2025. doi:10.1182/blood.2024027620.  
49 Facon T, Moreau P, Weisel K, et al. Supplement to: Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. Leukemia. 2025;39(4):942-950.  
50 San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood. 2021;139(4):492-501.  
51 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.  
52 Sborov D, Laubach J, Kaufman JL, et al. Daratumumab (DARA) + lenalidomide, bortezomib, and dexamethasone (RVd) in patients with transplant-eligible newly diagnosed multiple myeloma (NDMM): final analysis of GRIFFIN. Oral Presentation presented at: 19th International Myeloma Society (IMS) Annual Meeting; August 25-27, 2022; Los Angeles, CA.  
53 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.  
54 Kaufman JL, Usmani S, Miguel J, et al. Four-year follow-up of the phase 3 POLLUX study of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in relapsed or refractory multiple myeloma (RRMM). Poster presented at: 61st American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL.  
55 Mateos MV, Cavo M, Blade J, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020;395(10218):132-141.  
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