J&J Medical Connect
DARZALEX®

(daratumumab)

+ Save link

Medical inquiries

Connect with my medical science liaison

Connect with my medical science liaison

Chat live

Chat live

Available Monday - Friday 9AM - 4:30PM ET

Call me now

Call me now

Available Monday - Friday 9AM - 7:30PM ET

Email your inquiry

Email your inquiry

Call 1-800-526-7736

Call 1-800-526-7736

Available Monday - Friday 9AM - 8PM ET

Live video

Live video

Available Monday - Friday 9AM - 4:30PM ET

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

DARZALEX® (daratumumab)

Medical Information

DARZALEX - Minimal Residual Disease in Clinical Trials

Last Updated: 07/25/2025

SUMMARY

  • Janssen does not recommend the use of DARZALEX in a manner that is inconsistent with the approved labeling.
  • 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 complete response or better (≥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.
  • 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.7,20-28

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.

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 Subgroups29
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 Population29
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.

Results

Efficacy

MRD-Negativity Rates at Any Time During Maintenance and Follow-up in the mITT Population4,30
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 Population30
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 Population30
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 Population30
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 Population30
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).4,30
    • 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.30
  • Maintenance with DARZALEX improved PFS irrespective of induction/consolidation treatment and the post-consolidation MRD status.4,30
  • DARZALEX induction/consolidation improved PFS regardless of the cytogenetic risk status and revised ISS disease stage in the ITT population.4,30
  • DARZALEX maintenance improved PFS regardless of the cytogenetic risk status and revised ISS disease stage.4,30

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 Population30
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 Population30
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 Population30
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.

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.31 
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).6,31

Analysis of Clinically Important Subgroups of MAIA

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

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.

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.

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)32 presented updated efficacy and safety results after 2 years of maintenance therapy in this study. Sborov et al (2022)33 presented the final efficacy and safety results after all patients completed ≥1 year of follow-up after the end of study treatment.

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 Maintenance13,34
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,13,34
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).

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 18 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 MA, 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 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.  
21 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.  
22 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.  
23 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).  
24 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.  
25 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.  
26 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.  
27 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.  
28 Rodriguez-Otero P, Voorhees P, Boccadoro M, et al. Daratumumab for newly diagnosed multiple myeloma: pooled analysis of patients aged ≥65 years from GRIFFIN and PERSEUS. [Published online ahead of print April 11, 2025]. Clin Lymphoma Myeloma Leuk. doi:10.1016/j.clml.2025.04.007.  
29 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. Lancet Oncol. 2024;25(8):1003-1014.  
30 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.  
31 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.  
32 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.  
33 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.  
34 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.  
Endchat
Chat live