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DARZALEX®

(daratumumab)

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DARZALEX® (daratumumab)

Medical Information

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

Last Updated: 02/09/2026

Summary

  • Johnson & Johnson does not recommend the use of DARZALEX in a manner that is inconsistent with the approved labeling.
  • MAIA was 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 (2024)2 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 overall survival (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 [hazard ratio {HR}, 0.67; 95% confidence interval {CI}, 0.55-0.82; 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 was a phase 3 study evaluating the safety and efficacy of bortezomib, melphalan, and prednisone (VMP) alone vs DARZALEX + VMP (D-VMP) in patients with NDMM ineligible for high-dose chemotherapy with autologous stem cell transplant (ASCT).3
    • Mateos et al (2025)4 reported the final efficacy and safety analysis of the ALCYONE study at a median follow-up of 86.7 months. At the median follow-up, the median OS in the D-VMP vs VMP group was 83.0 months (95% CI, 72.5-not estimable [NE]) vs 53.6 months (95% CI, 46.3-60.9), respectively (HR, 0.65; 95% CI, 0.53-0.80; P<0.0001). The most common grade 3 or 4 treatment-emergent adverse events (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 was a phase 2 study evaluating the safety and efficacy of DARZALEX when administered in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd) for the treatment of multiple myeloma (MM) in patients who have not received previous treatment or have relapsed after receiving only 1 line of treatment.5
    • Yimer et al (2022)6 reported the end-of-study analysis of LYRA. At the end of cycle 4, very good partial response or better (≥VGPR) was achieved by 57.1% patients in the relapsed multiple myeloma (RMM) arm and 44.2% patients in the NDMM arm. The median progression-free survival (PFS) was 21.7 months in the RMM arm and not reached (NR) in the NDMM arm (both in patients who received and did not receive transplant). The overall response rate (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%).
  • Other relevant literature has been identified in addition to the data summarized above.7-15

CLINICAL DATA

DARZALEX in Combination With Lenalidomide and Dexamethasone

MAIA (MMY3008; NCT02252172) was an international, randomized, open-label, active-controlled, multicenter, phase 3 study in patients with NDMM not eligible for high dose chemotherapy and ASCT.1

Study Design/Methods

  • Primary endpoint: PFS1 
  • Key Secondary endpoints: Complete response or better (≥CR), ≥VGPR, minimal residual disease (MRD)-negativity (10-5), ORR, OS, and safety1 

Final Survival Analysis of the MAIA Study

Facon et al (2024)2 presented the updated OS results for the D-Rd vs Rd arm at a long-term median follow-up of 89.3 months.

Results

Patient Characteristics
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).
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.2
  • 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 (ITT Population; MAIA).2

Analysis of OS in Prespecified Patient Subgroups (ITT Population; MAIA)2
Subgroup
D-Rd
Rd
HR (95% CI)a
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 entryb
   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; 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.
aHR and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable. HR <1 indicates an advantage for D-Rd.
bCytogenetic 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).
  • 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 (Safety Population; MAIA).2
    • 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 those treated, 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 lines of therapy, 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, complete response or better (≥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.

Summary of First Subsequent Antimyeloma Therapy (Safety Population; MAIA)a,2
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.2 
    • Progressive disease 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 adverse events (AEs).
  • In the D-Rd vs Rd arm, 33% reduction in the risk of death was reported.2 

Summary of Death and Causes of Death (Safety Population; MAIA)a,2
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) was 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.3

Study Design/Methods

  • Primary endpoint: PFS3 
  • Secondary endpoints: ORR, ≥VGPR, ≥CR, MRD-negativity (10-5), OS3 

Final Efficacy and Safety Analysis of the ALCYONE Study

Mateos et al (2025)4 reported the final efficacy and safety analysis of the ALCYONE study at a median follow-up of 86.7 months.

Results

Patient Characteristic and Disposition

Baseline Demographics and Patient Characteristics (ITT Population; ALCYONE)a,16

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 (interquartile range [IQR], 14.5-77.3) vs 12.0 months (IQR, 7.2-12.0), respectively.4
  • Patient disposition in the ITT population is summarized in Table: Summary of Patient Disposition (ITT Population; ALCYONE).4,16

Summary of Patient Disposition (ITT Population; ALCYONE)4,16

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-NE) vs 53.6 months (95% CI, 46.3-60.9), respectively (HR, 0.65; 95% CI, 0.53-0.80; P<0.0001).4
    • 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 international staging system (ISS) stage III disease. Results of prespecified subgroup analyses for OS in the D-VMP and VMP groups are presented in Table: OS in Prespecified Subgroup (ALCYONE).4

OS in Prespecified Subgroups (ALCYONE)4 

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. The MRD status of the D-VMP and VMP groups is summarized in Table: Summary of MRD-Negativity Rates and Durable MRD-Negativity Rates (ITT Population; ALCYONE).4
  • 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).

Summary of MRD-Negativity Rates and Durable MRD-Negativity Rates (ITT Population; ALCYONE)4

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: CI, confidence interval; 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.4
    • The median time-to-subsequent antimyeloma therapy in the D-VMP vs VMP group was 66.8 months (95% CI, 47.9-NE) vs 25.9 months (95% CI, 23.4-28.6), respectively (HR, 0.37; 95% CI, 0.30-0.46; P<0.0001).
    • 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.
    • Details pertaining to subsequent antimyeloma therapies are summarized in Table: Summary of the Most Common Subsequent Antimyeloma Therapy in the Safety Population.4,16

Summary of The Most Commona Subsequent Antimyeloma Therapy in the Safety Population4,16
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.4
    • 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).4
Safety
  • No new safety concerns were identified with a longer follow-up.4
  • TEAEs were experienced by 98% of patients in the D-VMP group and 97% of patients in the VMP group. The most common TEAEs are summarized in Table: Summary of the Most Common TEAEs (ALCYONE).4
    • Grade 3 or 4 TEAEs occurred in 83% of patients receiving D-VMP and 77% of patients receiving VMP.4
    • The most common grade 3 or 4 infection in both treatment groups was pneumonia (D-VMP, 16%; VMP, 5%).4
    • 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.4
      • In the D-VMP group, IRRs of any grade and grade 3 and serious TEAEs were reported in <1% of patients.16
      • No IRR of any grade was reported in the VMP group.16
    • 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).16
    • 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 (ALCYONE).4,16 

Summary of the Most Common TEAEs (ALCYONE)4

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 TEAEs (ALCYONE)4,16
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.4
    • 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).4,16
  • Death due to adverse events was reported in 10% vs 6% of patients in the D-VMP vs VMP group, respectively.4
    • 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]).4

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. The search was limited to publications from 2020 to present.

References

Show
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2 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.  
3 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.  
4 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.  
5 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.  
6 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, 2018; San Diego, CA.  
7 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.  
8 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.  
9 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.  
10 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.  
11 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-.  
12 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.  
13 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.  
14 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.  
15 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.  
16 Mateos M, 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.