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

DARZALEX® (daratumumab)

Medical Information

Use of DARZALEX in Newly Diagnosed Multiple Myeloma in Patients Ineligible for Autologous Stem Cell Transplantation

Last Updated: 06/10/2025

Summary

  • Janssen does not recommend the use of DARZALEX in a manner that is inconsistent with the approved labeling.
  • MAIA is a phase 3 study evaluating the safety and efficacy of lenalidomide and dexamethasone (Rd) and DARZALEX in combination with Rd (D-Rd) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM)1
    • Facon et al (2019)1 reported the prespecified interim results of this ongoing study.
    • Facon et al (2025)2 reported the updated efficacy and safety results from the MAIA sstudy at a long-term median follow-up of 64.5 months. As of the clinical cutoff date of October 21, 2021, the median progression-free survival (PFS) was 61.9 months vs 34.4 months in the D-Rd vs Rd arm, respectively (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.45-0.67; P<0.0001). The median overall survival (OS) was not reached (NR) in the D-Rd arm and was 65.5 months in the Rd arm (HR, 0.66; 95% CI, 0.53-0.83; P=0.0003). The D-Rd vs Rd arm showed a significantly higher (all P<0.0001) overall response rate (ORR) (92.9% vs 81.6%), complete response (CR) or better (≥CR) rate (51.1% vs 30.1%), and very good partial response (VGPR) or better (≥VGPR) rate (81.5% vs 56.9%). Similarly, the D-Rd vs Rd arm showed a significantly higher (all P<0.0001) minimal residual disease (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]). No new safety concerns were observed with a longer follow-up. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 95.9% vs 88.8% of patients from the D-Rd vs Rd arm, respectively. The most common (≥20%) grade 3/4 TEAEs with D-Rd vs Rd were neutropenia (54.1% vs 37.0%, respectively) and anemia (17.0% vs 21.6%, respectively). Grade 3/4 infections occurred in 42.6% vs 29.6% of patients from the D-Rd vs Rd arm, respectively. Serious TEAEs occurred in 78.8% vs 71.0% of patients from the D-Rd vs Rd arm, respectively, with pneumonia being the most common serious TEAE (18.7% vs 10.7%, respectively). The overall discontinuation rate due to TEAEs was lower in the D-Rd vs Rd arm (14.6% vs 23.8%). TEAEs leading to death were reported in 9.9% vs 9.3% of patients from the D-Rd vs Rd arm, respectively.
    • Facon et al (2024)3 presented the results of the updated efficacy and safety analysis of the MAIA study. At a median follow-up of 89.3 months (range, 0-102.2), a 33% reduction in the risk of death was observed with the D-Rd vs Rd arms. Median OS was reached for the D-Rd arm and was prolonged for patients in the D-Rd vs Rd arms (90.3 vs 64.1 months [HR, 0.67; 95% CI, 0.55-0.82; nominal P<0.0001]). The median time to subsequent antimyeloma therapy was 42.4 months in the Rd arm and NR in the D-Rd arm (HR, 0.51; 95% CI, 0.41-0.63; nominal P<0.0001). Deaths were reported for 47.5% (n=173) of patients in the D-Rd arm and 59.7% (n=218) of patients in the Rd arm, mostly due to disease progression.
  • ALCYONE is a phase 3 study evaluating the safety and efficacy of bortezomib, melphalan, and prednisone (VMP) alone and DARZALEX + VMP (D-VMP) in patients with NDMM ineligible for high-dose chemotherapy with autologous stem cell transplant (ASCT).4
    • Mateos et al (2025)5 reported the final efficacy and safety analysis of the ALCYONE study at a median follow-up of 86.7 months (interquartile range [IQR], 28.5-85.2). The median PFS on the next line of therapy in the D-VMP vs VMP group was 66.7 months (95% CI, 58.6–80.1) vs 42.4 months (95% CI, 37.3-47.1), respectively (HR, 0.56; 95% CI, 0.46-0.68; P<0.0001). The MRD-negativity rate at 10-5 threshold in the D-VMP vs VMP group was 28% vs 7%, respectively (OR, 5.23; 95% CI, 3.27-8.36; P<0.0001). The most common grade 3 or 4 TEAEs in the D-VMP vs VMP group were neutropenia (40% vs 39%, respectively), thrombocytopenia (35% vs 38%, respectively), and anemia (18% vs 20%, respectively). Pneumonia was the most common grade 3 or 4 infection, reported by 16% of patients in the D-VMP group and 5% of patients in the VMP group.
  • LYRA is a phase 2 study evaluating the safety and efficacy of DARZALEX when administered in combination VCd for the treatment of MM in patients who have not received previous treatment or have relapsed after receiving only 1 line of treatment.6-8
    • Yimer et al (2022)8 reported the end-of-study analysis of LYRA. At the end of cycle 4, ≥VGPR was achieved by 57.1% patients in the relapsed multiple myeloma (RMM) arm and 44.2% patients in the NDMM arm. The median PFS was 21.7 months in the RMM arm and NR in the NDMM arm (both in patients who received and did not receive transplant). The ORR was 86% in the RMM arm, 97% in the NDMM transplant arm, and 83% in the NDMM non-transplant arm. The most frequent any-grade TEAE was fatigue (68.6%). Grade 3/4 TEAEs occurred in 62.8% of patients with the most frequent being neutropenia (12.8%).
  • EQUULEUS is a phase 1b multicenter study evaluating the safety and efficacy of DARZALEX when administered in combination with various treatment regimens, including KRd, for the treatment of NDMM for transplant eligible and non-eligible patients.9,10
  • Other relevant literature has been identified in addition to the data summarized above.11-19

PRODUCT LABELING

CLINICAL DATA

DARZALEX in Combination With Lenalidomide and Dexamethasone

MAIA (MMY3008; NCT02252172) is an international, randomized, open-label, active-controlled, multicenter, phase 3 study in patients with NDMM not eligible for high dose chemotherapy and ASCT (N=737).1 Facon et al (2021)20 reported the updated safety and efficacy results in the MAIA study at the prespecified interim OS analysis with a median follow-up of 56.2 months. Facon et al (2025)2 reported the updated efficacy and safety results from the MAIA study at a long-term median follow-up of 64.5 months. Facon et al (2024)3 presented updated efficacy and safety results at a median follow-up of 89.3 months.

Long-term Efficacy and Safety Analysis of the MAIA Study

Facon et al (2025)2 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

Demographic and Baseline Disease Characteristics of the ITT Population21
Characteristic
D-Rd
(n=368)
Rd
(n=369)
Age
   Median (range), years
73.0 (50-90)
74.0 (45-89)
ECOG PSa, n (%)
   0
127 (34.5)
123 (33.3)
   1
178 (48.4)
187 (50.7)
   ≥2
63 (17.1)
59 (16.0)
ISS disease stageb, n (%)
   I
98 (26.6)
103 (27.9)
   II
163 (44.3)
156 (42.3)
   III
107 (29.1)
110 (29.8)
Type of measurable disease, n (%)
   IgG
225 (61.1)
231 (62.6)
   IgA
65 (17.7)
66 (17.9)
   Otherc
9 (2.4)
10 (2.7)
   Detected in urine only
40 (10.9)
34 (9.2)
   Detected in serum FLC only
29 (7.9)
28 (7.6)
Cytogenetic riskd
   N
319
323
   Standard risk, n (%)
271 (85.0)
279 (86.4)
   High risk, n (%)
48 (15.0)
44 (13.6)
Median (range) time since initial diagnosis of MM, months
0.95 (0.1-13.3)
0.89 (0-14.5)
Abbreviations: del, deletion; D-Rd, DARZALEX + 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; Rd, lenalidomide + dexamethasone; t, translocation.
aECOG PS is scored on a scale of 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bISS disease stage was based on the combination of serum β2-microglobulin and albumin.
cIncludes IgD, IgE, IgM, and biclonal disease.
dCytogenetic risk was assessed by fluorescence in situ hybridization or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del(17p).

Demographic and Baseline Disease Characteristics Based on Age Subgroups21
Characteristic
<70 Years
≥70 to <75 Years
≥75 Years
≥80 Years
D-Rd
(n=78)
Rd
(n=77)
D-Rd
(n=130)
Rd
(n=131)
D-Rd
(n=160)
Rd
(n=161)
D-Rd
(n=66)
Rd
(n=71)
Age
   Median (range), years
68
(50-69)
68
(45-69)
72
(70-74)
72
(70-74)
78
(75-90)
79
(75-89)
82
(79-90)
82
(80-89)
ECOG PSa, n (%)
   0
34 (43.6)
28 (36.4)
42 (32.3)
48 (36.6)
51 (31.9)
47 (29.2)
21 (31.8)
18 (25.4)
   1
31 (39.7)
37 (48.1)
69 (53.1)
67 (51.1)
78 (48.8)
83 (51.6)
32 (48.5)
37 (52.1)
   ≥2
13 (16.7)
12 (15.6)
19 (14.6)
16 (12.2)
31 (19.4)
31 (19.3)
13 (19.7)
16 (22.5)
ISS disease stageb, n (%)
   I
31 (39.7)
25 (32.5)
34 (26.2)
41 (31.3)
33 (20.6)
37 (23.0)
13 (19.7)
13 (18.3)
   II
21 (26.9)
32 (41.6)
67 (51.5)
54 (41.2)
75 (46.9)
70 (43.5)
27 (40.9)
28 (39.4)
   III
26 (33.3)
20 (26.0)
29 (22.3)
36 (27.5)
52 (32.5)
54 (33.5)
26 (39.4)
30 (42.3)
Type of measurable disease, n (%)
   IgG
44 (56.4)
45 (58.4)
79 (60.8)
82 (62.6)
102 (63.8)
104 (64.6)
41 (62.1)
41 (57.7)
   IgA
13 (16.7)
18 (23.4)
26 (20.0)
21 (16.0)
26 (16.3)
27 (16.8)
13 (19.7)
10 (14.1)
   Otherc
2 (2.6)
1 (1.3)
2 (1.5)
4 (3.1)
5 (3.1)
5 (3.1)
2 (3.0)
4 (5.6)
   Detected in urine only
12 (15.4)
9 (11.7)
12 (9.2)
12 (9.2)
16 (10.0)
13 (8.1)
4 (6.1)
8 (11.3)
   Detected in serum FLC only
7 (9.0)
4 (5.2)
11 (8.5)
12 (9.2)
11 (6.9)
12 (7.5)
6 (9.1)
8 (11.3)
Cytogenetic riskd, n (%)
   N
66
66
112
119
141
138
57
60
   Standard risk
56 (84.8)
58 (87.9)
98 (87.5)
103 (86.6)
117 (83.0)
118 (85.5)
47 (82.5)
52 (86.7)
   High risk
10 (15.2)
8 (12.1)
14 (12.5)
16 (13.4)
24 (17.0)
20 (14.5)
10 (17.5)
8 (13.3)
Median (range) time since initial diagnosis of MM, months
0.85 (0.2-6.2)
0.82 (0.3-14.5)
0.90 (0.1-8.7)
0.95 (0.2-9.2)
0.95 (0.2-13.3)
0.92 (0.0-9.2)
1.02 (0.2-13.3)
0.95 (0.0-9.2)
Abbreviations: del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FLC, free light chain; Ig, immunoglobulin; ISS, International Staging System; MM, multiple myeloma; Rd, lenalidomide+dexamethasone; t, translocation.
aECOG PS is scored on a scale of 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bISS disease stage was based on the combination of serum β2-microglobulin and albumin.
cIncludes IgD, IgE, IgM, and biclonal disease.
dCytogenetic risk was assessed by fluorescence in situ hybridization or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del(17p).

Treatment Exposure in the Overall Safety Population21
Parameter
D-Rd
(n=364)
Rd
(n=365)
Median (range) number of treatment cycles
51 (1-83)
24 (1-82)
Relative dose intensity
DARZALEX
      n
364
0
      Median (range), %
98.0 (3.2-107.0)
-
Lenalidomide
      n
326
338
      Median (range), %
65.0 (7.9-202.1)
83.4 (4.8-239.3)
Dexamethasone
      n
364
365
      Median (range), %
76.5 (21.9-110.7)
84.8 (18.9-154.5)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone.

Patient Disposition and Treatment Discontinuation According to Age Group (MAIA - Long-term Follow-up)2,21
Parameter
<70 Years
≥70 to <75 Years
≥75 Years
≥80 Years
D-Rd (n=78)
Rd (n=77)
D-Rd (n=130)
Rd (n=131)
D-Rd (n=160)
Rd (n=161)
D-Rd (n=66)
Rd (n=71)
Patients treateda, n (%)
78
(100)
76
(98.7)
129
(99.2)
130
(99.2)
157
(98.1)
159
(98.8)
65
(98.5)
70
(98.6)
Patients who discontinued treatmentb, n (%)
37
(47.4)
64
(84.2)
79
(61.2)
106
(81.5)
117
(74.5)
141
(88.7)
44
(67.7)
64
(91.4)
   Reasons for discontinuation, n (%)
      PD
17 (21.8)
34 (44.7)
42 (32.6)
47 (36.2)
48 (30.6)
50 (31.4)
20 (30.8)
22 (31.4)
      AE
9 (11.5)
12 (15.8)
20 (15.5)
33 (25.4)
28 (17.8)
44 (27.7)
6 (9.2)
21 (30.0)
      Noncompliance with study drug
5 (6.4)
5 (6.6)
7 (5.4)
7 (5.4)
9 (5.7)
18 (11.3)
5 (7.7)
7 (10.0)
      Death
5 (6.4)
2 (2.6)
5 (3.9)
7 (5.4)
14 (8.9)
16 (10.1)
6 (9.2)
6 (8.6)
      Physician’s decision
1 (1.3)
9 (11.8)
3 (2.3)
7 (5.4)
12 (7.6)
8 (5.0)
3 (4.6)
6 (8.6)
      Patient withdrawal
0 (0)
2 (2.6)
1 (0.8)
3 (2.3)
1 (0.6)
3 (1.9)
0 (0)
0 (0)
      Lost to follow-up
0 (0)
0 (0)
0 (0)
0 (0)
1 (0.6)
2 (1.3)
1 (1.5)
2 (2.9)
      Other
0 (0)
0 (0)
1 (0.8)
2 (1.5)
4 (2.5)
0 (0)
3 (4.6)
0 (0)
Abbreviations: AE, adverse event; D-Rd, DARZALEX + lenalidomide + dexamethasone; PD, progressive disease; Rd, lenalidomide + dexamethasone.
aPercentages are based on the number of patients randomized.
bPercentages are based on the number of patients treated.
Efficacy
  • The median PFS was 61.9 months vs 34.4 months in the D-Rd vs Rd arm, respectively (HR, 0.55; 95% CI, 0.45-0.67; P<0.0001).2
  • The most common reasons for confirmed PD in each group were biochemical (D-Rd, 76.2%; Rd, 83.6%), bone lesions (D-Rd, 16.4%; Rd, 13.6%), plasmacytomas (D-Rd, 8.2%; Rd, 4.5%), and other causes (D-Rd, 1.6%; Rd, 2.3%).2
  • The median OS was NR in the D-Rd arm and was 65.5 months in the Rd arm (HR, 0.66; 95% CI, 0.53-0.83; P=0.0003).2
    • The estimated 60-month OS rate was 66.6% vs 53.6% in the D-Rd vs Rd arm, respectively.
    • OS improved with D-Rd vs Rd across subgroups of patients based on age as summarized in Table: PFS and OS Based on Age Subgroups:
    • The OS benefit with D-Rd vs Rd was consistent across prespecified patient subgroups based on baseline characteristics as presented in Table: Analysis of OS in Prespecified Patient Subgroups.
  • The D-Rd vs Rd arm showed a significantly higher (all P<0.0001) ORR (92.9% vs 81.6%), ≥CR rate (51.1% vs 30.1%), and ≥VGPR rate (81.5% vs 56.9%) as presented in Table: Response Rates in the ITT Population.
    • The ORR, ≥CR rate, and ≥VGPR rate were higher for the D-Rd vs Rd arm across all age subgroups and are summarized in Table: Response Rates Based on Age Subgroups.
    • The cumulative best response rate improved with continuous D-Rd treatment in patients who achieved ≥CR and ≥VGPR.
    • Continued D-Rd treatment markedly deepened the best response rate over time, with the ≥CR rate increasing from 8.2% by 6 months to 28.0% by 12 months, 40.8% by 18 months, 45.4% by 24 months, 48.1% by 30 months, and 51.1% by 48 months.
    • For patients who achieved ≥CR:
      • The median PFS was NR in either treatment arm (HR, 0.52; 95% CI, 0.35-0.76; P=0.0007).
      • The estimated 60-month PFS rate was 73.7% vs 53.8% in the D-Rd vs Rd arm, respectively.
      • The median OS was NR in either treatment arm (HR, 0.58; 95% CI, 0.37-0.91; P=0.0164).
      • The estimated 60-month OS rate was 81.7% vs 69.1% in the D-Rd vs Rd arm, respectively.
    • For patients who achieved VGPR:
      • The median PFS was 42.7 months vs 36.2 months in the D-Rd vs Rd, respectively (HR, 0.71; 95% CI, 0.51-0.99; P=0.0401).
      • The estimated 60-month PFS rate was 37.1% vs 23.2% in the D-Rd vs Rd arm, respectively.
      • The median OS was NR in the D-Rd arm and was 63.1 months in the Rd arm (HR, 0.78; 95% CI, 0.53-1.16; P=0.2256).
      • The estimated 60-month OS rate was 61.5% vs 53.0% in the D-Rd vs Rd arm, respectively.
  • The D-Rd vs Rd arm showed a significantly higher (all P<0.0001) MRD-negativity rate (10-5 sensitivity; 32.1% vs 11.1%) and sustained MRD-negativity rate (10-5 sensitivity; ≥12 months, 18.8% vs 4.1%; ≥18 months, 16.8% vs 3.3%) as summarized in Table: Response Rates in the ITT Population.2
    • 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 as summarized in Table: Response Rates Based on Age Subgroups.
    • 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.
  • A total of 128 (35.2%) vs 194 (53.2%) patients from the D-Rd vs Rd arm, respectively, received subsequent therapy.2
    • In the D-Rd vs Rd arm, 9.4% vs 23.2% of patients received DARZALEX-containing treatment as their first subsequent therapy, respectively.
    • In the D-Rd vs Rd arm, 14.1% vs 48.5% of patients received DARZALEX-containing treatment as any subsequent line of therapy, respectively.
    • PFS on next line of therapy was 73.7 months vs 48.9 months in the D-Rd vs Rd arm, respectively (HR, 0.61; 95% CI, 0.49-0.76; P<0.0001).

Analysis of PFS in Prespecified Patient Subgroupsa,21
Subgroup
D-Rd
Rd
HR (95% CI)b
n/N
Median PFS, Months
n/N
Median PFS, Months
Sex
   Male
91/189
61.9
120/195
32.3
0.57 (0.44-0.76)
   Female
85/179
62.1
108/174
35.4
0.54 (0.40-0.71)
Age
   <75 years
89/208
NE
122/208
37.5
0.52 (0.39-0.68)
   ≥75 years
87/160
54.3
106/161
31.4
0.59 (0.44-0.79)
Race
   White
161/336
61.9
208/339
34.5
0.55 (0.45-0.67)
   Other
15/32
62.1
20/30
30.4
0.59 (0.30-1.16)
Region
   North America
49/101
58.2
60/102
30.4
0.57 (0.39-0.83)
   Other
127/267
61.9
168/267
36.9
0.55 (0.43-0.69)
Baseline renal function (CrCl)
   >60 mL/min
94/206
73.7
136/227
37.4
0.54 (0.41-0.70)
   ≤60 mL/min
82/162
56.7
92/142
29.7
0.55 (0.41-0.75)
Baseline hepatic function
   Normal
157/335
62.8
211/340
33.8
0.52 (0.43-0.65)
   Impaired
19/31
29.2
17/29
35.1
0.99 (0.51-1.91)
ISS disease stage
   I
38/98
NE
48/103
52.5
0.65 (0.42-1.00)
   II
77/163
63.8
107/156
29.7
0.46 (0.34-0.62)
   III
61/107
42.4
73/110
24.2
0.61 (0.43-0.86)
Type of MM
   IgG
112/225
60.7
135/231
38.7
0.69 (0.53-0.88)
   Non-IgG
34/74
63.8
53/76
23.5
0.39 (0.25-0.60)
Cytogenetic risk at study entry
   High riskc
28/48
45.3
31/44
29.6
0.57 (0.34-0.96)
   Standard risk
126/271
63.8
174/279
34.4
0.51 (0.41-0.64)
ECOG PS
   0
54/127
NE
74/123
39.6
0.51 (0.36-0.72)
   1
90/178
58.2
113/187
35.1
0.58 (0.44-0.77)
   ≥2
32/63
48.4
41/59
23.5
0.56 (0.35-0.89)
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IgG, immunoglobulin G; ISS, International Staging System; ITT, intention-to-treat; MM, multiple myeloma; NE, not estimable; PFS, progression-free survival; Rd, lenalidomide + dexamethasone; t, translocation.
aAnalysis of PFS in subgroups of the ITT population, which were defined according to baseline characteristics.
bHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable. HR <1 indicates an advantage for D-Rd.
cPatients at a high cytogenetic risk tested positive for ≥1 of the following cytogenetic abnormalities on fluorescence in situ hybridization or karyotype testing: del(17p), t(14;16), or t(4;14).

Analysis of OS in Prespecified Patient Subgroupsa,21
Subgroup
D-Rd
Rd
HR (95% CI)b
n/N
Median OS, Months
n/N
Median OS, Months
Sex
   Male
76/189
NE
101/195
61.0
0.71 (0.53-0.96)
   Female
56/179
73.7
75/174
68.6
0.63 (0.45-0.89)
Age
   <75 years
59/208
NE
90/208
NE
0.59 (0.43-0.83)
   ≥75 years
73/160
73.7
86/161
54.8
0.75 (0.55-1.02)
Race
   White
120/336
NE
158/339
66.4
0.69 (0.54-0.87)
   Other
12/32
NE
18/30
49.1
0.52 (0.25-1.07)
Region
   North America
36/101
NE
52/102
54.8
0.60 (0.39-0.92)
   Other
96/267
NE
124/267
66.9
0.70 (0.54-0.91)
Baseline renal function (CrCl)
   >60 mL/min
70/206
NE
102/227
68.6
0.67 (0.49-0.90)
   ≤60 mL/min
62/162
NE
74/142
54.8
0.65 (0.46-0.90)
Baseline hepatic function
   Normal
117/335
NE
164/340
65.4
0.63 (0.50-0.80)
   Impaired
15/31
66.1
12/29
NE
1.23 (0.57-2.63)
ISS disease stage
   I
21/98
NE
29/103
NE
0.71 (0.40-1.24)
   II
60/163
73.7
79/156
61.7
0.62 (0.44-0.87)
   III
51/107
66.1
68/110
47.3
0.69 (0.48-1.00)
Type of MM
   IgG
83/225
NE
102/231
68.6
0.78 (0.58-1.04)
   Non-IgG
26/74
NE
40/76
53.7
0.54 (0.33-0.88)
Cytogenetic risk at study entry
   High riskc
27/48
55.6
28/44
42.5
0.81 (0.48-1.38)
   Standard risk
90/271
NE
131/279
65.5
0.62 (0.48-0.81)
ECOG PS
   0
28/127
NE
41/123
NE
0.62 (0.38-1.01)
   1
73/178
73.7
96/187
58.3
0.70 (0.51-0.95)
   ≥2
31/63
61.9
39/59
39.0
0.61 (0.38-0.97)
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IgG, immunoglobulin G; ISS, International Staging System; ITT, intention-to-treat; MM, multiple myeloma; NE, not estimable; OS, overall survival; Rd, lenalidomide + dexamethasone; t, translocation.
aAnalysis of OS in subgroups of the ITT population, which were defined according to baseline characteristics.
bHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable. HR <1 indicates an advantage for D-Rd.
cPatients at a high cytogenetic risk tested positive for ≥1 of the following cytogenetic abnormalities on fluorescence in situ hybridization or karyotype testing: del(17p), t(14;16), or t(4;14).

Response Rates in the ITT Population2
Response, n (%)
D-Rd
(n=368)
Rd
(n=369)
P Value
ORR
342 (92.9)
301 (81.6)
<0.0001a
   ≥CR
188 (51.1)
111 (30.1)
<0.0001a
      sCR
131 (35.6)
58 (15.7)
<0.0001a
      CR
57 (15.5)
53 (14.4)
-
  ≥VGPR
300 (81.5)
210 (56.9)
<0.0001a
      VGPR
112 (30.4)
99 (26.8)
-
   PR
42 (11.4)
91 (24.7)
-
SD
11 (3.0)
55 (14.9)
-
PD
1 (0.3)
0 (0)
-
NE
14 (3.8)
13 (3.5)
-
MRD-negativity response rate (10-5 sensitivity), n (%)
118 (32.1)
41 (11.1)
<0.0001b
Sustained MRD-negativity response rate (10-5 sensitivity), n (%)
≥12 months
69 (18.8)
15 (4.1)
<0.0001b
≥18 months
62 (16.8)
12 (3.3)
<0.0001b
Abbreviations: CR, complete response; D-Rd, DARZALEX + lenalidomide + dexamethasone; ITT, intention-to-treat; NE, not estimable; ORR, overall response rate; PD, progressive disease; PR, partial response; Rd, lenalidomide + dexamethasone; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.
aP value was calculated using the Cochran-Mantel-Haenszel chi-square test.
bP value was calculated using the Fisher’s exact test.

Response Rates Based on Age Subgroups2
Response, n (%)
Age <70 Years
Age ≥70 to <75 Years
Age ≥75 Years
Age ≥80 Years
D-Rd
(n=78)
Rd
(n=77)
P Value
D-Rd
(n=130)
Rd
(n=131)
P Value
D-Rd
(n=160)
Rd
(n=161)
P Value
D-Rd
(n=66)
Rd
(n=71)
P Value
ORR
73 (93.6)
62 (80.5)
0.0156a
125 (96.2)
108 (82.4)
0.0004a
144 (90.0)
131 (81.4)
0.0275a
59 (89.4)
55 (77.5)
0.0629a
   ≥CR
44 (56.4)
24 (31.2)
0.0016a
73 (56.2)
41 (31.3)
<0.0001a
71 (44.4)
46 (28.6)
0.0033a
29 (43.9)
15 (21.1)
0.0044a
      sCR
31 (39.7)
11 (14.3)
0.0004a
50 (38.5)
23 (17.6)
0.0002a
50 (31.3)
24 (14.9)
0.0005
23 (34.8)
8 (11.3)
0.0010a
      CR
13 (16.7)
13 (16.9)
-
23 (17.7)
18 (13.7)
-
21 (13.1)
22 (13.7)
-
6 (9.1)
7 (9.9)
-
   ≥VGPR
64 (82.1)
45 (58.4)
0.0013a
111 (85.4)
76 (58.0)
<0.0001a
125 (78.1)
89 (55.3)
<0.0001a
50 (75.8)
31 (43.7)
0.0001a
      VGPR
20 (25.6)
21 (27.3)
-
38 (29.2)
35 (26.7)
-
54 (33.8)
43 (26.7)
-
21 (31.8)
16 (22.5)
-
   PR
9 (11.5)
17 (22.1)
-
14 (10.8)
32 (24.4)
-
19 (11.9)
42 (26.1)
-
9 (13.6)
24 (33.8)
-
SD
1 (1.3)
14 (18.2)
-
3 (2.3)
20 (15.3)
-
7 (4.4)
21 (13.0)
-
3 (4.5)
11 (15.5)
-
PD
0 (0)
0 (0)
-
0 (0)
0 (0)
-
1 (0.6)
0 (0)
-
0 (0)
0 (0)
-
NE
4 (5.1)
1 (1.3)
-
2 (1.5)
3 (2.3)
-
8 (5.0)
9 (5.6)
-
4 (6.1)
5 (7.0)
-
MRD-negativity response rate, n (%)
28 (35.9)
9 (11.7)
0.0006
47 (36.2)
16 (12.2)
0.0001
43 (26.9)
16 (9.9)
0.0001
17 (25.8)
4 (5.6)
0.0016
Abbreviations: CR, complete response; D-Rd, DARZALEX + lenalidomide + dexamethasone; MRD, minimal residual disease; NE, not estimable; ORR, overall response rate; PD, progressive disease; PR, partial response; Rd, lenalidomide + dexamethasone; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.
aP value was calculated using the Cochran-Mantel-Haenszel chi-square test.

PFS and OS Based on Age Subgroups2
Parameter
Age <70 Years
Age ≥70 to <75 Years
Age ≥75 Years
Age ≥80 Years
D-Rd
(n=78)
Rd
(n=77)
HR (95% CI)
P Value
D-Rd
(n=130)
Rd
(n=131)
HR (95% CI)
P Value
D-Rd
(n=160)
Rd
(n=161)
HR (95% CI)
P Value
D-Rd
(n=66)
Rd
(n=71)
HR (95% CI)
P Value
PFS
Median, months
NR
39.2
0.35 (0.21-0.56)
<0.0001
61.9
37.5
0.64 (0.45-0.89)
0.0079
54.3
31.4
0.59 (0.44-0.79)
0.0003
52.2
30.4
0.48 (0.31-0.76)
0.0011
OS
   Median, months
-
-
0.50 (0.27-0.90)
0.0179
-
-
0.64 (0.43-0.96)
0.0274
-
-
0.75 (0.55-1.02)
0.0671
-
-
0.71 (0.44-1.14)
0.1574
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HR, hazard ratio; NR, not reachable; OS, overall survival; Rd, lenalidomide + dexamethasone.
Safety
  • At clinical cutoff, 52 patients from the D-Rd arm discontinued lenalidomide ± dexamethasone but remained on the rest of the study treatment; 46 (88.5%) of these patients discontinued due to AEs.2
    • The median time to lenalidomide discontinuation was 37.8 months (range, 1-70).
    • The median duration of DARZALEX treatment was 66.2 months (range, 56-77).
    • The estimated 60-month PFS and OS rates were 98.1% and 100.0%, respectively.
    • Of the aforementioned 52 patients, 13 (25.0%) discontinued lenalidomide but continued DARZALEX + dexamethasone and 39 (75.0%) discontinued lenalidomide + dexamethasone and continued DARZALEX monotherapy.
      • In the 39 patients who discontinued lenalidomide + dexamethasone and continued DARZALEX monotherapy, the median time to discontinuation was 39.1 months (range, 3-67) and the median DARZALEX treatment duration was 65.6 months (range, 56-73). The estimated 60-month PFS and OS rates were 97.4% and 100.0%, respectively.
      • One patient in the D-Rd arm stopped DARZALEX after 15 days due to AEs but continued lenalidomide treatment without progression at the clinical cutoff.
  • No new safety concerns were observed with a longer follow-up.2
    • Grade 3/4 TEAEs occurred in 95.9% vs 88.8% of patients from the D-Rd vs Rd arm, respectively.
    • Grade 3/4 infections occurred in 42.6% vs 29.6% of patients from the D-Rd vs Rd arm, respectively.
    • Serious TEAEs occurred in 78.8% vs 71.0% of patients from the D-Rd vs Rd arm, respectively, with pneumonia being the most common serious TEAE (18.7% vs 10.7%, respectively).
      • Among patients aged ≥75 years, serious TEAEs occurred in 80.9% vs 79.2% of patients from the D-Rd vs Rd arm, respectively, with pneumonia being the most common serious TEAE (19.7% vs 12.6%, respectively).
      • Among patients aged ≥80 years, serious TEAEs occurred in 81.5% vs 82.9% of patients from the D-Rd vs Rd arm, respectively, with pneumonia being the most common serious TEAE (24.6% vs 8.6%, respectively).
    • The overall discontinuation rate due to TEAEs was lower in the D-Rd vs Rd arm (14.6% vs 23.8%).
      • Discontinuation of lenalidomide due to TEAEs was reported in 36.8% vs 24.4% of patients from the D-Rd vs Rd arm, respectively.
      • Discontinuation of dexamethasone due to TEAEs was reported in 39.8% vs 36.2% of patients from the D-Rd vs Rd arm, respectively.
      • Discontinuation of DARZALEX due to TEAEs was reported in 14.6% of patients.
      • Among patients aged ≥75 years, treatment discontinuation due to TEAEs was reported in 15.3% vs 27.7% of patients from the D-Rd vs Rd arm, respectively.
      • Among patients aged ≥80 years, treatment discontinuation due to TEAEs was reported in 6.2% vs 20.0% of patients from the D-Rd vs Rd arm, respectively.
    • TEAEs leading to death were reported in 9.9% vs 9.3% of patients from the D-Rd vs Rd arm, respectively.
      • Among patients aged ≥75 years, TEAEs leading to death were reported in 11.5% vs 13.2% of patients from the D-Rd vs Rd arm, respectively.
      • Among patients aged ≥80 years, TEAEs leading to death were reported in 12.3% vs 11.4% of patients from the D-Rd vs Rd arm, respectively.

Most Common Any-Grade or Grade 3/4 TEAEs in the Safety Populationa,2
TEAE, n (%)
D-Rd (n=364)
Rd (n=365)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Hematologic
   Neutropenia
224 (61.5)
197 (54.1)
166 (45.5)
135 (37.0)
   Anemia
154 (42.3)
62 (17.0)
150 (41.1)
79 (21.6)
Nonhematologic
   Diarrhea
240 (65.9)
33 (9.1)
188 (51.5)
22 (6.0)
   Fatigue
164 (45.1)
33 (9.1)
114 (31.2)
17 (4.7)
   Constipation
157 (43.1)
6 (1.6)
137 (37.5)
2 (0.5)
   Peripheral edema
155 (42.6)
10 (2.7)
117 (32.1)
3 (0.8)
   Back pain
155 (42.6)
14 (3.8)
109 (29.9)
14 (3.8)
   Asthenia
136 (37.4)
19 (5.2)
101 (27.7)
18 (4.9)
   Nausea
133 (36.5)
7 (1.9)
88 (24.1)
2 (0.5)
   Insomnia
125 (34.3)
11 (3.0)
116 (31.8)
14 (3.8)
   Bronchitis
124 (34.1)
12 (3.3)
87 (23.8)
7 (1.9)
   Cough
123 (33.8)
2 (0.5)
65 (17.8)
0 (0.0)
   Dyspnea
119 (32.7)
12 (3.3)
63 (17.3)
4 (1.1)
   Pneumonia
113 (31.0)
71 (19.5)
66 (18.1)
39 (10.7)
   Weight decreased
112 (30.8)
10 (2.7)
69 (18.9)
11 (3.0)
   Peripheral sensory neuropathy
111 (30.5)
9 (2.5)
66 (18.1)
2 (0.5)
   Muscle spasms
111 (30.5)
2 (0.5)
86 (23.6)
5 (1.4)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event.
aAny-grade TEAEs that are listed are those that occurred in ≥30% of patients in either group.

Most Common Any-Grade or Grade 3/4 TEAEs Among Patients Aged ≥75 Years and ≥80 Years in the Safety Populationa,21
TEAE, n (%)
Patients Aged ≥75 years
Patients Aged ≥80 years
D-Rd (n=157)
Rd (n=159)
D-Rd (n=65)
Rd (n=70)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Hematologic
   Neutropenia
109 (69.4)
98
(62.4)
81
(50.9)
66
(41.5)
45
(69.2)
37
(56.9)
34
(48.6)
26
(37.1)
   Anemia
71 (45.2)
32 (20.4)
73 (45.9)
40 (25.2)
31 (47.7)
12 (18.5)
35 (50.0)
19 (27.1)
   Thrombocytopenia
39 (24.8)
16 (10.2)
43 (27.0)
19 (11.9)
21 (32.3)
7 (10.8)
20 (28.6)
8 (11.4)
   Lymphopenia
37 (23.6)
33 (21.0)
25 (15.7)
20 (12.6)
10 (15.4)
8 (12.3)
13 (18.6)
10 (14.3)
Nonhematologic
   Diarrhea
98 (62.4)
16 (10.2)
80 (50.3)
8 (5.0)
37 (56.9)
5 (7.7)
35 (50.0)
3 (4.3)
   Peripheral edema
76 (48.4)
6 (3.8)
53 (33.3)
2 (1.3)
31 (47.7)
0 (0.0)
24 (34.3)
2 (2.9)
   Constipation
75 (47.8)
2 (1.3)
61 (38.4)
1 (0.6)
27 (41.5)
0 (0.0)
27 (38.6)
1 (1.4)
   Fatigue
73 (46.5)
15 (9.6)
48 (30.2)
8 (5.0)
26 (40.0)
7 (10.8)
19 (27.1)
3 (4.3)
   Back pain
65 (41.4)
7 (4.5)
53 (33.3)
6 (3.8)
24 (36.9)
2 (3.1)
21 (30.0)
2 (2.9)
   Asthenia
58 (36.9)
8 (5.1)
43 (27.0)
10 (6.3)
25 (38.5)
3 (4.6)
26 (37.1)
8 (11.4)
   Weight decreased
49 (31.2)
6 (3.8)
31 (19.5)
5 (3.1)
19 (29.2)
2 (3.1)
16 (22.9)
2 (2.9)
   Bronchitis
48 (30.6)
7 (4.5)
31 (19.5)
4 (2.5)
18 (27.7)
2 (3.1)
15 (21.4)
1 (1.4)
   Nausea
48 (30.6)
2 (1.3)
40 (25.2)
0 (0.0)
21 (32.3)
1 (1.5)
20 (28.6)
0 (0.0)
   Pneumonia
44 (28.0)
32 (20.4)
33 (20.8)
23 (14.5)
22 (33.8)
17 (26.2)
13 (18.6)
8 (11.4)
   Pyrexia
44 (28.0)
6 (3.8)
22 (13.8)
3 (1.9)
20 (30.8)
4 (6.2)
7 (10.0)
0 (0.0)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event.
aAny-grade TEAEs that are listed are those that occurred in ≥30% of patients in either group.

Final Survival Analysis of the MAIA Study

Facon et al (2024)3 presented the updated OS results for the D-Rd vs Rd arm at a long-term median follow-up of around 7.5 years.

Results

Patient Characteristics
Efficacy
  • At a median follow-up of 89.3 months (range, 0-102.2), the 7-year OS rate was 53.1% for the D-Rd arm and 39.3% for the Rd arm.
  • Median OS was reached for the D-Rd group and was prolonged for patients in the D-Rd vs Rd arm (90.3 vs 64.1 months [HR, 0.67; 95% CI, 0.55-0.82; nominal P<0.0001]). See Table: Analysis of OS in PreSpecified Patient Subgroups.
  • Median time to subsequent antimyeloma therapy was 42.4 months in the Rd arm and NR in the D-Rd arm (HR, 0.51; 95% CI, 0.41-0.63; nominal P<0.0001). See Table: Summary of First Subsequent Antimyeloma Therapy in the Safety Population.
    • In the D-Rd vs Rd arm, 10.7% (15/140) vs 24.4% (49/201) of patients received DARZALEX-containing regimens as their first subsequent therapy.
    • Among treated patients, 38.5% (140/364) vs 55.1% (201/365) of patients in the D-Rd vs Rd arm received ≥1 subsequent antimyeloma therapy.
    • Across subsequent therapy lines, the most common antineoplastic agents in the D-Rd vs Rd arms were bortezomib (27.7% vs 41.9%), DARZALEX (6.3% vs 28.8%), and carfilzomib (7.7% vs 12.3%).
    • In patients evaluable for best response to first subsequent antimyeloma therapy, ≥CR was achieved by 4.6% (6/130) vs 4.1% (8/193) in the D-Rd vs Rd arm, and ≥VGPR was achieved by 13.8% (18/130) vs 23.8% (46/193) of patients in the D-Rd vs Rd arm.
    • No patient in either group reported the use of B-cell maturation antigen (BCMA)- or G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted therapy.
    • Investigational drug was given to 2 patients in the D-Rd group and 2 patients in the Rd group in subsequent therapy lines.

Analysis of OS in PreSpecified Patient Subgroupsa,3
Subgroup
D-Rd
Rd
HR (95% CI)b
n/N
Median OS, Months
n/N
Median OS, Months
Sex
   Male
95/189
82.5
120/195
60.6
0.72 (0.55-0.94)
   Female
80/179
NE
98/174
67.8
0.66 (0.49-0.89)
Age
   <75 years
84/208
NE
107/208
79.6
0.69 (0.52-0.92)
   ≥75 years
91/160
72.3
111/161
54.8
0.67 (0.51-0.88)
Race
   White
161/336
92.7
197/339
65.5
0.71 (0.57-0.87)
   Other
14/32
90.3
21/30
49.1
0.50 (0.25-0.99)
Region
   North America
46/101
92.7
64/102
54.8
0.57 (0.39-0.83)
   Other
129/267
90.3
154/267
66.8
0.74 (0.58-0.93)
Baseline renal function (CrCl)
   >60 mL/min
99/206
92.7
123/227
69.9
0.78 (0.60-1.01)
   ≤60 mL/min
76/162
90.3
95/142
54.4
0.57 (0.42-0.77)
Baseline hepatic function
   Normal
156/335
NE
203/340
63.8
0.65 (0.53-0.80)
   Impaired
19/31
63.5
15/29
87.4
1.31 (0.66-2.58)
ISS disease stage
   I
34/98
NE
42/103
NE
0.79 (0.50-1.24)
   II
77/163
92.7
95/156
61.7
0.63 (0.46-0.85)
   III
64/107
65.2
81/110
47.3
0.68 (0.49-0.95)
Type of MM
   IgG
111/225
87.2
132/231
69.3
0.78 (0.60-1.00)
   Non-IgG
35/74
86.4
49/76
53.7
0.58 (0.37-0.89)
Cytogenetic risk at study entryc
   High risk
31/48
55.6
36/44
42.5
0.65 (0.40-1.06)
   Standard risk
122/271
NE
160/279
65.5
0.66 (0.52-0.84)
ECOG PS
   0
48/127
NE
56/123
NE
0.76 (0.52-1.12)
   1
86/178
92.7
118/187
58.3
0.64 (0.48-0.84)
   ≥2
41/63
62.8
44/59
39.0
0.68 (0.44-1.04)
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IgG, immunoglobulin G; ISS, International Staging System; MM, multiple myeloma; NE, not estimable; OS, overall survival; Rd, lenalidomide + dexamethasone; t, translocation.
aIn the ITT population, which included all randomized patients.
bHR and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable. HR <1 indicates an advantage for D-Rd.
cCytogenetic risk was based on fluorescence in situ hybridization or karyotype analysis; patients who had a high-risk cytogenetic profile had ≥1 of the following high-risk abnormalities: del(17p), t(14;16), or t(4;14).

Summary of First Subsequent Antimyeloma Therapy in the Safety Populationa,3
n (%)
D-Rd
(n=140)
Rd
(n=201)
First subsequent therapy classb,c
   PI only
69 (49.3)
101 (50.2)
   IMiD only
22 (15.7)
25 (12.4)
   PI + IMiD
25 (17.9)
16 (8.0)
   DARZALEX monotherapy or combination
15 (10.7)
49 (24.4)
   Other
9 (6.4)
10 (5.0)
Most common first subsequent therapy regimensb,d
   Bortezomib/cyclophosphamide/dexamethasone
19 (13.6)
29 (14.4)
   Bortezomib/dexamethasone
20 (14.3)
28 (13.9)
   Bortezomib/melphalan/prednisone
14 (10.0)
28 (13.9)
   DARZALEX/bortezomib/dexamethasone
4 (2.9)
27 (13.4)
   Lenalidomide/dexamethasone
13 (9.3)
16 (8.0)
   Bortezomib/pomalidomide/dexamethasone
9 (6.4)
3 (1.5)
   Bortezomib/lenalidomide/dexamethasone
8 (5.7)
3 (1.5)
   DARZALEX/lenalidomide/dexamethasone
4 (2.9)
6 (3.0)
   Pomalidomide/dexamethasone
2 (1.4)
6 (3.0)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; IMiD, immunomodulatory drugs; PI, proteasome inhibitor; Rd, lenalidomide + dexamethasone.
aThe safety population included all randomized patients who received ≥1 dose of study treatment.
bPercentages were calculated with the number of patients who received subsequent therapy in each treatment group as the denominator.
cTherapy classes are mutually exclusive. Patients in any therapy class subgroup may have received additional agents (other than PI, IMiD, or DARZALEX), such as dexamethasone.
dRegimens received by ≥3% of patients in either treatment group.
Safety and Tolerability
  • Among the safety population, 78.3% (n=285) of patients in the D-Rd arm and 94.5% (n=345) in the Rd arm discontinued study treatment.
    • PD was the primary reason for discontinuation in both the D-Rd (32.7%) and Rd arms (38.6%).
    • A lower proportion of patients in the D-Rd (16.5%) and Rd arms (25.8%) discontinued study treatment due to AEs.
  • In the D-Rd vs Rd arm, 33% reduction in the risk of death was reported.

Summary of Death and Causes of Death in the Safety Populationa,3
n (%)
D-Rd
(n=364)
Rd
(n=365)
Total number of patients who died during the study
173 (47.5)
218 (59.7)
   Primary cause of death
      Disease progression
76 (20.9)
88 (24.1)
      Adverse events
44 (12.1)
40 (11.0)
         Related to study treatmentb
14 (3.8)
10 (2.7)
         Unrelated to study treatment
28 (7.7)
29 (7.9)
         Othersc
53 (14.6)
90 (24.7)
         Infections/infestations
9 (2.5)
30 (8.2)
         General disorders/administration site conditionsd
11 (3.0)
5 (1.4)
         Neoplasms (benign, malignant, or unspecified)
11 (3.0)
4 (1.1)
         Cardiac disorders
1 (0.3)
8 (2.2)
         Nervous system disorders
3 (0.8)
5 (1.4)
         Unknown
13 (3.6)
27 (7.4)
Deaths within 30 days of last study treatment dose
31 (8.5)
35 (9.6)
   Primary cause of death
      Disease progression
1 (0.3)
1 (0.3)
      Adverse events
29 (8.0)
32 (8.8)
         Related to study treatmentb
11 (3.0)
10 (2.7)
         Unrelated to study treatment
18 (4.9)
22 (6.0)
         Othere
1 (0.3)
2 (0.5)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone.
aThe safety population included all randomized patients who received ≥1 dose of study treatment.
bAdverse events were related to ≥1 of the 3 components of study treatment: DARZALEX, lenalidomide, and dexamethasone.
cOther reasons were reported in ≥1% of patients in either treatment group.
dAll events were related to the general health condition of the patient.
eIncludes a nervous system disorder in 1 patient in the D-Rd group and a blood and lymphatic system disorder and general disorder/administration site condition in 1 patient each in the Rd group.

DARZALEX in Combination With Bortezomib, Melphalan, and Prednisone

ALCYONE (MMY3007; NCT02195479) is a multicenter, randomized, open-label, active-controlled, phase 3 study evaluating 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.4 Mateos et al (2018)4reported results of a planned interim analysis from the ALCYONE study with a median follow-up of 16.5 months. Results of the updated analysis is summarized below. Mateos et al (2025)5 reported the final efficacy and safety analysis at a median follow-up of 86.7 months. Results from the final analysis are summarized below.

Results

Patient Characteristic and Disposition

Baseline Demographics and Patient Characteristics in The ITT Populationa,22

Characteristic
D-VMP
(n=350)
VMP
(n=356)
Total
(N=706)
Age
   Median (range), years
71 (40-93)
71 (50-91)
71 (40-93)
   Distribution, n (%)
      <65 years
36 (10)
24 (7)
60 (8)
      65-74 years
210 (60)
225 (63)
435 (62)
      ≥75 years
104 (30)
107 (30)
211 (30)
Sexb, n (%)
   Male
160 (46)
167 (47)
327 (46)
   Female
190 (54)
189 (53)
379 (54)
Raceb, n (%)
   White
297 (85)
304 (85)
601 (85)
   Asian
47 (13)
45 (13)
92 (13)
   Black or African American
3 (1)
3 (1)
6 (1)
   Otherc
1 (<1)
3 (1)
4 (1)
   Unknown/not reported
2 (1)
1 (<1)
3 (<1)
Ethnicity, n (%)
   Hispanic or Latino
24 (7)
16 (4)
40 (6)
   Not Hispanic or Latino
320 (91)
332 (93)
652 (92)
   Unknown/not reported
6 (2)
8 (2)
14 (2)
ECOG performance statusd, n (%)
   0
78 (22)
99 (28)
177 (25)
   1
182 (52)
173 (49)
355 (50)
   2
90 (26)
84 (24)
174 (25)
ISS disease stagee, n (%)
   I
69 (20)
67 (19)
136 (19)
   II
139 (40)
160 (45)
299 (42)
   III
142 (41)
129 (36)
271 (38)
Cytogenetic risk profilef, n/n (%)
   Standard risk
261/314 (83)
257/302 (85)
518/616 (84)
   High-risk
53/314 (17)
45/302 (15)
98/616 (16)
Median time since diagnosis of multiple myeloma (range), months
0.76 (0.1-11.4)
0.82 (0.1-25.3)
0.79 (0.1-25.3)
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; ITT, intention-to-treat; VMP, bortezomib + melphalan + prednisone.
aThe ITT population was defined as all patients who were randomized.
bSex and race were self-reported by patients.
cPatients reporting multiple races.
dThe ECOG performance status is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
eThe ISS disease stage is based on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease.
fCytogenetic risk was assessed by fluorescence in situ hybridization or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del(17p).
  • At the final analysis clinical cutoff date of May 31, 2023, the median duration of treatment in the D-VMP vs VMP group was 33.0 months (IQR, 14.5-77.3) vs 12.0 months (IQR, 7.2-12.0), respectively.5
  • Patient disposition in the ITT population is summarized in Table: Summary of Patient Disposition.

Summary of Patient Disposition5,22

Parameter
D-VMP
(n=350)
VMP
(n=356)
Patients treated, n (%)
346 (99)
354 (99)
Patients still on treatment, n (%)
76 (22)
0 (0)
Patients who discontinued treatment, n (%)
270 (78)
118 (33)
Reason for discontinuation
   Progressive disease, n (%)
167 (48)
47 (13)
   Adverse event, n
32
34
   Death, n
28
8
   Noncompliance with study drug, n
16
15
   Patient withdrawal, n
15
6
   Physician decision, n
4
7
   Lost to follow-up, n
2
0
   Other, n
6
1
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; VMP, bortezomib + melphalan + prednisone.
Efficacy
  • At a median follow-up of 86.7 months, the median OS in the D-VMP vs VMP group was 83.0 months (95% CI, 72.5-not estimable) vs 53.6 months (95% CI, 46.3-60.9), respectively (HR, 0.65; 95% CI, 0.53-0.80; P<0.0001).5
    • Details regarding patients censored for OS are summarized in Table: Summary of Reasons for Censoring of OS in the ITT Population.
    • A prespecified subgroup analysis of OS indicated a nonsignificant trend favoring D-VMP vs VMP in patients ≥75 years of age and other subgroups with poor prognosis, such as those with renal impairment or ISS stage III disease.5 Results of prespecified subgroup analyses for OS in the D-VMP and VMP groups are presented in Table: OS in Prespecified Subgroups.

Summary of Reasons for Censoring of OS in The ITT population22

Parameter, n (%)
D-VMP
(n=350)
VMP
(n=356)
Patients censored
178 (51)
139 (39)
   Reason for censoring
      Other
134 (38)
90 (25)
         End of data collection
130 (37)
87 (24)
      Withdrawal by patient
29 (8)
30 (8)
      Lost to follow-up
15 (4)
18 (5)
      Physician decision
0
1 (<1)
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ITT, intention-to-treat; OS, overall survival; VMP, bortezomib + melphalan + prednisone.

OS in Prespecified Subgroups5 

Subgroup
D-VMP
VMP
HR (95% CI)
Events/patients
n/N
Median
(95% CI), Months
Events/patients
n/N
Median
(95% CI), Months
All patients
172/350
83.0 (72.5-NE)
217/356
53.6 (46.3-60.9)
0.65 (0.53-0.80)
Sex
   Male
84/160
72.7 (60.3-89.1)
99/167
50.7 (42.3-68.5)
0.71 (0.53-0.95)
   Female
88/190
89.2 (74.1-NE)
118/189
55.1 (46.9-64.8)
0.60 (0.46-0.79)
Age
   <75 years
112/246
89.2 (78.7-NE)
144/249
56.6 (47.7-69.4)
0.62 (0.48-0.79)
   ≥75 years
60/104
59.1 (50.7-82.7)
73/107
49.7 (39.2-57.5)
0.74 (0.53-1.04)
Race
   White
154/297
80.1 (63.6-89.1)
191/304
52.9 (45.7-58.8)
0.67 (0.54-0.83)
   Other
18/53
NE (72.7-NE)
26/52
78.1 (39.6-NE)
0.54 (0.29-0.98)
Region
   Europe
149/289
81.0 (63.8-89.1)
187/295
53.6 (45.7-58.9)
0.67 (0.54-0.83)
   Other
23/61
NE (69.7-NE)
30/61
57.9 (39.6-NE)
0.57 (0.33-0.99)
Baseline renal function (CrCl)
   >60 mL/min
99/200
85.9 (64.5-NE)
119/211
57.9 (47.9-72.6)
0.72 (0.55-0.94)
   ≤60 mL/min
73/150
80.1 (63.6-NE)
98/145
48.1 (38.0-56.0)
0.56 (0.41-0.76)
Baseline hepatic functiona
   Normal
151/304
82.7 (69.7-NE)
181/304
55.7 (48.1-66.4)
0.68 (0.55-0.85)
   Impaired
21/46
85.9 (44.6-NE)
36/52
40.7 (26.5-56.0)
0.49 (0.28-0.84)
ISS disease stageb
   I
19/69
94.4 (94.4-NE)
27/67
NE (67.0-NE)
0.53 (0.29-0.95)
   II
68/139
83.0 (59.5-NE)
96/160
61.3 (50.7-78.1)
0.70 (0.51-0.96)
   III
85/142
63.6 (52.9-79.2)
94/129
42.3 (36.0-46.9)
0.60 (0.45-0.81)
Type of MM
   IgG
105/207
81.0 (62.9-NE)
133/218
58.2 (46.9-69.4)
0.70 (0.54-0.90)
   Non-IgG
48/82
72.5 (54.4-85.9)
52/83
46.2 (42.7-56.6)
0.73 (0.49-1.08)
Cytogenetic risk at study entryc
   High-risk
35/53
46.2 (26.7-72.5)
31/45
39.5 (31.6-54.1)
0.91 (0.56-1.47)
   Standard risk
122/261
85.9 (78.7-NE)
156/257
55.1 (48.1-66.4)
0.59 (0.47-0.75)
ECOG PS
   0
26/78
NE (83.0-NE)
58/99
53.7 (43.9-75.7)
0.40 (0.25-0.63)
   1-2
146/272
72.5 (59.2-85.9)
159/257
52.9 (45.2-58.9)
0.72 (0.58-0.90)
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IgG, immunoglobulin G; ISS, International Staging System; MM, multiple myeloma; NE, not estimable; OS, overall survival; ULN, upper limit of normal; VMP, bortezomib + melphalan + prednisone.
aImpaired baseline hepatic function includes mild (total bilirubin ≤ULN and aspartate aminotransferase >ULN or total bilirubin >ULN but ≤1.5× ULN), moderate (total bilirubin >1.5× ULN but ≤3× ULN), and severe (total bilirubin >3× ULN).
bThe ISS disease stage is derived based on the combination of serum β2-microglobulin and albumin concentrations.
cHigh-risk cytogenetics are defined either by fluorescence in situ hybridization testing [t(4;14), t(14;16), or del(17p)] or by karyotype testing [t(4;14) or del(17p)].
  • The MRD-negativity rate (at the 10-5 and 10-6 sensitivity levels) was higher in the D-VMP group than in the VMP group. Compared with the VMP group, the D-VMP group had a higher durable MRD-negativity rate (10-5 sensitivity level) for ≥6 and ≥12 months.5 The MRD status of the D-VMP and VMP groups is summarized in Table: Summary of MRD-Negativity Rates and Durable MRD-Negativity Rates in the ITT Population.
  • In the D-VMP and VMP groups, a longer OS was observed in patients who were MRD-negative (HR, 0.60; 95% CI, 0.31-1.14) than in patients who were not MRD-negative (HR, 0.77; 95% CI, 0.62-0.95).5

Summary of MRD-Negativity Rates and Durable MRD-Negativity Rates in the ITT Population5

Parameter
D-VMP
(n=350)
VMP
(n=356)
OR
(95% CI)a,b
P Valuec
MRD-negativity, n (%)
   10-5
99 (28.3)
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: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ITT, intent-to-treat; MRD, minimal residual disease; VMP, bortezomib + melphalan + prednisone; OR, odds ratio.
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 randomised. An OR greater than 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 greater than 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.
  • In the ITT population, 46% vs 72% of patients in the D-VMP vs VMP group, respectively were initiated on subsequent antimyeloma therapy or died from progressive disease without subsequent treatment.5
    • The median time-to-subsequent antimyeloma therapy in the D-VMP vs VMP group was 66.8 months (95% CI, 47.9-not estimable) vs 25.9 months (95% CI, 23.4-28.6), respectively (HR, 0.37; 95% CI, 0.30-0.46; P<0.0001).5
    • A total of 12 (3%) of 346 patients in the D-VMP group and 93 (26%) of 354 patients in the VMP group received DARZALEX as a subsequent antimyeloma therapy.5
    • Details pertaining to subsequent antimyeloma therapies are summarized in Table: Summary of the Most Common Subsequent Antimyeloma Therapy in the Safety Population.

Summary of The Most Commona Subsequent Antimyeloma Therapy in the Safety Population5,22
Parameter, n (%)
D-VMP
(n=346)
VMP
(n=354)
Total
(N=700)
Patients receiving ≥1 subsequent antimyeloma therapy
150 (43)
243 (69)
393 (56)
   Most common first subsequent therapy regimens
      Lenalidomide/dexamethasone
47 (14)
77 (22)
124 (18)
      Carfilzomib/lenalidomide/dexamethasone
18 (5)
15 (4)
33 (5)
      Lenalidomide/dexamethasone/ixazomib
16 (5)
8 (2)
24 (3)
      Bortezomib/dexamethasone
7 (2)
3 (1)
10 (1)
      Thalidomide/cyclophosphamide/dexamethasone
6 (2)
17 (5)
23 (3)
      Bortezomib/cyclophosphamide/dexamethasone
5 (1)
9 (3)
14 (2)
      Lenalidomide/dexamethasone/elotuzumab
2 (1)
8 (2)
10 (1)
      DARZALEX/lenalidomide/dexamethasone
1 (<1)
25 (7)
26 (4)
      DARZALEX/bortezomib/dexamethasone
0
11 (3)
11 (2)
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; VMP, bortezomib + melphalan + prednisone.
aMost common defined as ≥2% of patients in either treatment group.
  • PFS events on the subsequent line of therapy were reported in 53% vs 67% of patients in the D-VMP vs VMP group, respectively.5
    • The median PFS on the next line of therapy in the D-VMP vs VMP group was 66.7 months (95% CI, 58.6-80.1) vs 42.4 months (95% CI, 37.3-47.1), respectively (HR, 0.56; 95% CI, 0.46-0.68; P<0.0001).5
Safety
  • No new safety concerns were identified with a longer follow-up.5
  • TEAEs were experienced by 98% of patients in the D-VMP group and 97% of patients in the VMP group.5 The most common TEAEs are summarized in Table: Summary of the Most Common TEAEs.
    • Grade 3 or 4 TEAEs occurred in 83% of patients receiving D-VMP and 77% of patients receiving VMP.5
    • The most common grade 3 or 4 infection in both treatment groups was pneumonia (D-VMP, 16%; VMP, 5%).5
    • Infusion-related reactions (IRRs) of any grade were reported in 29% of patients in the D-VMP group, including a grade 3 reaction in 4% and a grade 4 reaction in 1% of patients.5
      • In the D-VMP group, IRRs of any grade and grade 3 and serious TEAEs were reported in <1% of patients.22
      • No IRR of any grade was reported in the VMP group.22
    • The D-VMP group experienced a higher rate of serious TEAEs compared with the VMP group (21% vs 16%, respectively). The most common serious TEAE observed in the D-VMP vs VMP group was pneumonia (5% vs 2%, respectively).22
    • The rate of treatment discontinuation due to TEAEs was 9% in both the D-VMP and VMP groups and are detailed in Table: Summary of Treatment Discontinuation Due to TEAEs.

Summary of the Most Common TEAEs5

Event, n (%)
D-VMP
(n=346)
VMP
(n=354)
Any Gradea
Grade 1-2
Grade
3
Grade
4
Grade
5
Any Gradea
Grade
1-2
Grade
3
Grade
4
Grade
5
Any TEAEs
338 (98)
47
(14)
184
(53)
77
(22)
30
(9)
342 (97)
65
(18)
180
(51)
77
(22)
20
(6)
Hematologic AE
   Neutropenia
175 (51)
35
(10)
107 (31)
33
(10)
0
186 (53)
48
(14)
103
(29)
35
(10)
0
   Thrombocytopenia
173 (50)
53
(15)
83
(24)
37
(11)
0
190 (54)
56
(16)
83
(23)
51
(14)
0
   Anemia
112 (32)
49
(14)
61
(18)
2
(1)
0
131 (37)
61
(17)
68
(19)
2
(1)
0
Nonhematological AE
   Peripheral sensory
   neuropathy
100 (29)
95
(27)
4
(1)
1
(<1)
0
122
(34)
108
(31)
14
(4)
0
0
   Diarrhea
101 (29)
92
(27)
9
(3)
0
0
87
(25)
76
(21)
11
(3)
0
0
   Pyrexia
89
(26)
87
(25)
2
(1)
0
0
74
(21)
72
(20)
2
(1)
0
0
   Nausea
76
(22)
73
(21)
3
(1)
0
0
76
(21)
72
(20)
4
(1)
0
0
   Back pain
73
(21)
65
(19)
8
(2)
0
0
42
(12)
38
(11)
4
(1)
0
0
   Cough
71
(21)
70
(20)
1
(<1)
0
0
27
(8)
26
(7)
1
(<1)
0
0
   Upper respiratory
   tract infection
107 (31)
99
(29)
7
(2)
0
1
(<1)
50
(14)
44
(12)
6
(2)
0
0
   Bronchitis
77
(22)
66
(19)
11
(3)
0
0
27
(8)
24
(7)
3
(1)
0
0
   Pneumonia
78
(23)
19
(5)
53
(15)
4
(1)
2
(1)
 19
(5)
3
(1)
15
(4)
1
(<1)
0
Abbreviations: AE, adverse event; D-VMP, DARZALEX + bortezomib + melphalan + prednisone; TEAE, treatment-emergent adverse event; VMP, bortezomib + melphalan + prednisone.
aPreferred terms for any grade of TEAEs with an occurrence of ≥20% are reported.

Summary of Treatment Discontinuation Due to TEAEs5,22
TEAEs
D-VMP
(n=346)
VMP
(n=354)
Patients with TEAEs leading to treatment discontinuation, n (%)
31 (9)
33 (9)
TEAEs leading to treatment discontinuationa, n (%)
   Pneumonia
4 (1)
1 (<1)
   Upper respiratory tract infection
2 (1)
0
   Acute respiratory failure
2 (1)
0
   Fatigue
1 (<1)
2 (1)
   Peripheral sensory neuropathy
0
6 (2)
   Neuralgia
0
2 (1)
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; TEAE, treatment-emergent adverse event; VMP, bortezomib + melphalan + prednisone.
aTEAEs leading to treatment discontinuation in at least 2 patients in either treatment group are reported.
  • The incidence of second primary malignancies in the D-VMP vs VMP group was 8% vs 6%, respectively.5
    • The most frequently reported second primary malignancies in the D-VMP vs VMP group were basal cell carcinoma (1.2% vs 0.6%, respectively) and myelodysplastic syndrome (1.2% vs 0.6%, respectively).5,22
  • Death due to adverse events was reported in 10% vs 6% of patients in the D-VMP vs VMP group, respectively.5
    • Deaths due to an adverse event considered related to at least 1 of 4 study treatment components occurred in 5 (1%) of 346 D-VMP patients (due to pneumonia, acute myocardial infarction, neuroendocrine tumor, tumor lysis syndrome, and acute respiratory failure [one each]) and in 3 (1%) of 354 VMP patients (due to acute myeloid leukemia, pulmonary embolism, and bacterial pneumonia [one each]).5

Predictive and Prognostic Role of MRD-Negativity and Durability - Analysis of ALCYONE

San-Miguel et al (2021)17 evaluated the predictive and prognostic role of MRD-negativity and durability in patients with NDMM ineligible for transplant.

Results

Patient Characteristics

Demographics and Baseline Characteristics by MRD Durability17
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, n (%)
      <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, n (%)
   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, n
314
88
46
42
302
23
9
14
   Standard-risk
   cytogenetic
   abnormality, n (%)
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, n (%)
53 (16.9)
14 (15.9)
6 (13)
8 (19)
45 (14.9)
4 (17.4)
2 (22.2)
2 (14.3)
      del(17p), n (%)
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; del, deletion; 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.
  • 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 (ITT Population).
  • Estimated 36-month PFS on next line of therapy (PFS2) rate (ITT; D-VMP, n=350; VMP, n=356)23:
    • MRD-negative (10-5) 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 NDMM17
MRD-negativity (10-5)
(N=706)
D-VMP
VMP
P Valuea
ITT
n=350
n=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
n=160
n=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 (ITT Population)17
Estimated 36-month time to subsequent anticancer therapy rate, %
D-VMP (n=350)
VMP
(n=356)
MRD-negative (10-5) at ≥1 time point, n (%)
94 (88.7)
25 (75.3)
MRD-positive, n (%)
256 (54.9)
331 (33.2)
Achieved and remained MRD-negative (10-5) for ≥6 months, n (%)
55 (96.3)
16 (93.8)
MRD-negativity not ≥6 months, n (%)
39 (77.2)
9 (38.9)
Achieved and remained MRD-negative (10-5) for ≥12 months, n (%)
49 (95.8)
10 (100)
MRD-negativity not ≥12 months, n (%)
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.

LITERATURE SEARCH

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 05 June 2025.

 

References

Show
1 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.  
2 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.  
3 Facon T, Kumar SK, Orlowski R, et al. Final survival analysis of daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma: MAIA study. Poster presented at: The European Hematology Association (EHA) Hybrid Congress; June 13-16, 2024; Madrid, Spain.  
4 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.  
5 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.  
6 Yimer H, Melear J, Faber E, et al. Daratumumab, bortezomib, cyclophosphamide and dexamethasone in newly diagnosed and relapsed multiple myeloma: LYRA study. Brit J Haematol. 2019;185(3):492-502.  
7 Yimer H, Melear J, Faber E, et al. LYRA: a phase 2 study of daratumumab (dara) plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in newly diagnosed and relapsed patients (Pts) with multiple myeloma (MM). Poster presented at: The 60th American Society of Hematology (ASH) Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA.  
8 Yimer H, Melear J, Faber E, et al. LYRA: A phase 2 study of daratumumab (dara) plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in newly diagnosed and relapsed patients (Pts) with multiple myeloma (MM). Oral Presentation presented at: 60th American Society of Hematology (ASH) Annual Meeting & Exposition; December 1-4; San Diego, CA.  
9 Chari A, Lonial S, Martinez-Lopez J, et al. Final analysis of a phase 1b study of daratumumab in combination with carfilzomib and dexamethasone for relapsed or refractory multiple myeloma (RRMM). presented at: 61st American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL.  
10 Chari A, Usmani S, Krishnan A, et al. Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients with newly diagnosed multiple myeloma (MMY1001): updated results from an open-label, phase 1b study. Poster presented at: 59th American Society of Hematology (ASH) Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA.  
11 Fu W, Bang SM, Huang H, et al. Subgroup analyses of progression-free survival from the phase 3 OCTANS and ALCYONE studies in transplant-ineligible patients with newly diagnosed multiple myeloma treated with bortezomib, melphalan, and prednisone with or without daratumumab. Poster presented at: 65th American Society of Hematology (ASH) Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA.  
12 Fu W, Huang H, Li W, et al. Efficacy and safety of daratumumab, bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) in Chinese patients with newly diagnosed multiple myeloma: OCTANS. Oral presentation presented at: 18th International Myeloma Workshop (IMW); September 8-11, 2021; Vienna, Austria.  
13 Hou J, Fu W, Bang SM, et al. Daratumumab, bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone in transplant-ineligible patients with newly diagnosed multiple myeloma: pooled analysis of OCTANS and ALCYONE. Poster presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual.  
14 Wang J, Fu W, Bang SM, et al. Progression-free survival outcomes by response status for bortezomib, melphalan, and prednisone with or without daratumumab in newly diagnosed multiple myeloma: pooled subgroup analysis of OCTANS and ALCYONE. Poster presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual.  
15 Jakubowiak AJ, Kumar S, Medhekar R, et al. Daratumumab Improves Depth of Response and Progression-free Survival in Transplant-ineligible, High-risk, Newly Diagnosed Multiple Myeloma. Oncol. 2022;27(7):oyac067-.  
16 Sanchez LJ, Moshier E, Lieberman-Cribbin A, et al. A phase 2 study of daratumumab in combination with dose-attenuated bortezomib, lenalidomide, and dexamethasone in transplant ineligible older adults with newly diagnosed multiple myeloma. Abstract presented at: The 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2024; San Diego, CA.  
17 San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity with daratumumab in newly diagnosed multiple myeloma: MAIA and ALCYONE. Blood. 2022;139:492-501.  
18 Fu W, Bang SM, Huang H, et al. Bortezomib, melphalan, and prednisone with or without daratumumab in transplant-ineligible Asian patients with newly diagnosed multiple myeloma: the phase 3 OCTANS study. Clin Lymphoma Myeloma Leuk. 2023;23:446-455 e4.  
19 Fu W, Bang SM, Huang H, et al. Daratumumab, bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) alone in transplant-ineligible Asian patients with newly diagnosed multiple myeloma: final analysis of the phase 3 OCTANS study. Poster presented at: The 65th American Society of Hematology (ASH) Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA.  
20 Facon T, Kumar S, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596.  
21 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.  
22 Mateos MV, San-Miguel J, Cavo M, et al. Supplement to: 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.  
23 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.  
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