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DARZALEX® (daratumumab)

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DARZALEX - ALCYONE Study

Last Updated: 01/27/2026

SUMMARY

  • 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 newly diagnosed multiple myeloma (NDMM) who were ineligible for high-dose chemotherapy with autologous stem-cell transplantation (ASCT).1
    • Mateos et al (2025)2 reported the final efficacy and safety analysis results of the ALCYONE study at a median follow-up of 86.7 months. The median progression-free survival (PFS) on the next line of therapy in the D-VMP vs VMP group was 66.7 months (95% confidence interval [CI], 58.6-80.1) vs 42.4 months (95% CI, 37.3-47.1), respectively (hazard ratio [HR], 0.56; 95% CI, 0.46-0.68; P<0.0001). The most common grade 3/4 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 3/4 infection, reported in 16% of patients in the D-VMP group and 5% of patients in the VMP group.
  • Mateos et al (2021)3 conducted a subgroup analysis of frailty status in patients enrolled in the ALCYONE study. The overall response rate (ORR) was higher in the D-VMP arm vs VMP arm across frailty subgroups. For frail patients, ORR was achieved by 88.3% (n=144) patients in the D-VMP arm vs 72.4% (n=110) patients in the VMP arm (P=0.0003). The most common grade 3/4 TEAEs were neutropenia (nonfrail: 39.2% [D-VMP] and 42.4% [VMP]; frail: 41.3% and 34.4%) and thrombocytopenia (nonfrail: 32.8% and 36.9%; frail: 36.9% and 39.1%).
  • Other relevant literature has been identified in addition to the data summarized above.4-10 

CLINICAL DATA

ALCYONE (MMY3007; NCT02195479) is an open-label, active controlled, multicenter, randomized, phase 3 study evaluating the safety and efficacy of D-VMP vs VMP in patients with NDMM who were ineligible for high-dose chemotherapy with ASCT.1

Study Design/Methods

  • Patients were randomly assigned 1:1 to receive either VMP alone or D-VMP as follows (randomization was stratified according to disease stage [I, II, or III], geographic region [Europe vs other], and age [<75 vs ≥75 years])1:
    • VMP: up to 9 cycles (each 42-day) of:
      • Bortezomib 1.3 mg/m2 subcutaneously (SC) twice weekly on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2-9
      • Melphalan 9 mg/m2 orally once daily on days 1-4 of each cycle
      • Prednisone 60 mg/m2 orally once daily on days 1-4 of each cycle
    • D-VMP: Up to 9 cycles (each 42-day) of VMP as described above plus:
      • DARZALEX 16 mg/kg intravenously (IV) once weekly in cycle 1, once every 3 weeks in cycles 2-9, and once every 4 weeks thereafter until there was disease progression or unacceptable toxicity.
      • Patients in this arm also received dexamethasone 20 mg orally or IV and other pre-infusion medications (approximately 1 hour before DARZALEX infusion) for management of infusion reactions. On day 1 of each cycle, the dexamethasone 20 mg dose was substituted for the prednisone dose in the VMP regimen.
  • Patients with documented NDMM and who were not candidates for high-dose chemotherapy with ASCT because of coexisting conditions or older age (≥65 years) were included.1 
  • Primary endpoint: PFS1 
  • Key secondary endpoints: ORR, rates of very good partial response or better (≥VGPR), complete response or better (≥CR), minimal residual disease (MRD) negativity status, and overall survival (OS)1 
  • Other endpoints: safety, side-effect profile, time to response (TTR), and duration of response (DOR)1 

Final Efficacy and Safety Analysis of ALCYONE

Mateos et al (2025)2  reported the final efficacy and safety analysis results at a median follow-up of 86.7 months.

Results

Patient Characteristics and Disposition

Baseline Demographics and Patient Characteristics in the ITT Populationa,11
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 0-5, 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 hybridisation or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del(17p).

Summary of Patient Disposition2,11
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 (IQR, 28.5-85.2), 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).2
    • A prespecified subgroup analysis of OS indicated a nonsignificant trend favoring
      D-VMP vs VMP group in patients ≥75 years of age and other subgroups with poor prognosis, such as those with renal impairment or 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 Subgroups in the ITT Population.2 

OS in Prespecified Subgroups in the ITT Population2 
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 performance status
   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 in the ITT Population.2
  • 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 that in patients who were not MRD-negative (HR, 0.77; 95% CI, 0.62-0.95).2

Summary of MRD-Negativity Rates and Durable MRD-Negativity Rates in the ITT Population2
Parameter
D-VMP
(n=350)
VMP
(n=356)
OR
(95% CI)a,b
P Valuec
MRD-negativity, n (%)
   10-5
99 (28)
25 (7)
5.23 (3.27-8.36)
<0.0001
   10-6
33 (9)
3 (1)
12.96 (3.85-43.57)
<0.0001
Durable MRD-negativity (10-5)d, n (%)
   ≥6 months
56 (16)
16 (4)
4.05 (2.27-7.21)
<0.0001
   ≥12 months
49 (14)
10 (3)
5.63 (2.80-11.31)
<0.0001
Abbreviations: CI, confidence interval; D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ISS, International Staging System; ITT, intention-to-treat; MRD, minimal residual disease; OR, odds ratio; VMP, bortezomib + melphalan + prednisone.
aMantel-Haenszel estimate of the common OR for stratified tables was used for the MRD status. The stratification factors were as follows: ISS disease stage (I, II, or III), region (Europe vs other), and age (<75 years vs ≥75 years) as randomized. An OR of greater than 1 indicates an advantage for D-VMP.
bA Mantel-Haenszel estimate of the common OR without stratification was used for the durable MRD status.
An OR greater than 1 indicates an advantage for D-VMP.
cP values were derived from a Fisher’s exact test.
dDurable MRD-negativity was defined as the absence of MRD confirmed at least 6 or 12 months apart without any instances of MRD-positivity in between the 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.2
    • 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).2
    • Overall, 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.2
    • Details pertaining to subsequent antimyeloma therapies in the safety population are summarized in Table: Summary of the Most Common Subsequent Antimyeloma Therapies in the Safety Population.2,11
    • PFS events on the subsequent line of therapy were reported in 53% vs 67% of patients in the D-VMP vs VMP group, respectively.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).2

Summary of the Most Commona Subsequent Antimyeloma Therapies in the Safety Population2,11
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.
Safety
  • No new safety concerns were identified with a longer follow-up.
  • 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.2
    • Grade 3 or 4 TEAEs occurred in 83% of patients receiving D-VMP and 77% of patients receiving VMP.2
    • The most common grade 3 or 4 infection in both treatment groups was pneumonia (D-VMP, 16%; VMP, 5%).2
    • 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.2
      • In the D-VMP group, IRRs of any grade, grade 3 and serious TEAE were reported in <1% of patients.11
      • No IRR of any grade was reported in the VMP group.11
    • The D-VMP group experienced a higher rate of serious TEAEs compared to the VMP group (21% vs 16%). The most common serious TEAE observed in D-VMP vs VMP group was pneumonia (5% vs 2%).2
  • The rate of treatment discontinuation due to TEAEs was 9% in both the D-VMP and VMP groups. TEAEs in both groups are detailed in Table: Summary of Treatment Discontinuation Due to TEAEs.2,11

Summary of the Most Common TEAEs2
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: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; TEAE, treatment-emergent adverse event; VMP, bortezomib + melphalan + prednisone; AE, adverse event.
aPreferred terms for any grade of TEAEs with an occurrence of ≥20% are reported.

Summary of Treatment Discontinuation Due to TEAEs2,11
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; ITT, intent to treat; MRD, minimal residual disease; VMP, bortezomib + melphalan + prednisone; TEAE, treatment-related adverse event.
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.2
    • 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).2,11
  • 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 [1 each]) and in 3 (1%) of 354 VMP patients (due to acute myeloid leukemia, pulmonary embolism, and bacterial pneumonia [1 each]).2

Impact of Frailty on Safety and Efficacy in the ALCYONE Study

Mateos et al (2021)3 conducted a subgroup analysis of frailty status in patients enrolled in the ALCYONE study.

Study Design/Methods

  • Based on the retrospective frailty assessment conducted, patients were classified as fit (0), intermediate (1), or frail (≥2) based on age, Charlson Comordibity Index and baseline Eastern Cooperative Oncology Group performance status (ECOG PS) score. Non-frail subgroup was defined as patients who had a frailty score of fit or intermediate.3 

Results

Patient Characteristics
  • Median duration of follow-up was 40.1 months.3 
  • All patients (D-VMP, n=350; VMP, n=356) were stratified based on frailty status3:
    • Frail patients (n=315; 44.6%): 163 (46.6%) in the D-VMP arm vs 152 (42.7%) in the VMP arm.
    • Non-frail patients (n=391; 55.4%): 187 (53.4%) in the D-VMP arm vs 204 (57.3%) in the VMP arm.
  • The baseline characteristics based on frailty scores for D-VMP vs VMP is presented in the Table: Key Demographics and Baseline Characteristics by Frailty Status (ALCYONE).3 

Key Demographics and Baseline Characteristics by Frailty Status (ALCYONE)3
Non-Fraila
Frail
Fit (n=122)
Intermediate (n=269)
Total Non-Fraila (n=391)
Frail (n=315)
D-VMP (n=48)
VMP (n=74)
D-VMP (n=139)
VMP (n=130)
D-VMP (n=187)
VMP (n=204)
D-VMP (n=163)
VMP (n=152)
Age, years, n (%)
  Median (range)
70.0
(65-75)
71.0
(56-75)
71.0
(52-80)
70.0
(52-80)
70.0
(52-80)
70.0
(52-80)
74.0
(40-93)
74.0
(50-91)
    <65
0
3 (4.1)
13 (9.4)
10 (7.7)
13 (7.0)
13 (6.4)
23 (14.1)
11 (7.2)
    65-<75
45 (93.8)
60 (81.1)
105 (75.5)
98 (75.4)
150 (80.2)
158 (77.5)
60 (36.8)
67 (44.1)
    ≥75
3 (6.3)
11 (14.9)
21 (15.1)
22 (16.9)
24 (12.8)
33 (16.2)
80 (49.1)
74 (48.7)
    ≥80
0
0
1 (0.7)
3 (2.3)
1 (0.5)
3 (1.5)
32 (19.6)
29 (19.1)
ECOG PS score, n (%)
    0
48 (100)
74 (100)
18 (12.9)
17 (13.1)
66 (35.3)
91 (44.6)
12 (7.4)
8 (5.3)
    1
0
0
121 (87.1)
113 (86.9)
121 (64.7)
113 (55.4)
61 (37.9)
60 (39.5)
    2
0
0
0
0
0
0
90 (55.2)
84 (55.3)
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ECOG PS, Eastern Cooperative Oncology Group performance status; VMP, bortezomib + melphalan + prednisone.
aTotal non frail consists of fit and intermediate patients.
Efficacy
  • The median relative dose intensity of daratumumab was comparable across the frailty subgroups (non-frail, 99.3%; frail, 98.5%).3 
  • PFS benefit was observed in all subgroups3:
    • For total non-frail patients, median PFS was 45.7 months in the D-VMP arm vs 19.1 months in the VMP arm (HR, 0.36; 95% CI, 0.28-0.47; P<0.0001).
      • For fit patients, median PFS was not reached in the D-VMP arm vs 22.2 months in the VMP arm (HR, 0.34; 95% CI, 0.20-0.57; P<0.0001).
      • For intermediate patients, median PFS was 40.1 months in the D-VMP arm vs 18.3 months in the VMP arm (HR, 0.37; 95% CI, 0.27-0.50; P<0.0001).
    • For frail patients, median PFS was 32.9 months in the D-VMP arm vs 19.5 months in the VMP arm (HR, 0.51; 95% CI, 0.39-0.68; P<0.0001).
  • OS benefit was maintained in all subgroups3:
    • For total non-frail patients, median OS was not reached in both arms (HR, 0.52; 95% CI, 0.34-0.79; P=0.0017).
      • For fit patients, median OS was not reached in the D-VMP arm vs 46.2 months in the VMP arm (HR, 0.18; 95% CI, 0.05-0.62; P=0.0021).
      • For intermediate patients, median OS was not reached in both arms (HR, 0.62; 95% CI, 0.39-0.98; P=0.0407).
    • For frail patients, median OS was not reached in both arms (HR, 0.66; 95% CI, 0.46-0.96; P=0.0292).
  • The ORR was higher in the D-VMP arm vs VMP arm across frailty subgroups (ITT population)3:
    • For total non-frail patients, ORR was achieved by 93.0% (n=174) in the D-VMP arm vs 75.0% (n=153) in the VMP arm (P<0.0001).
    • For frail patients, ORR was achieved by 88.3% (n=144) patients in the D-VMP arm vs 72.4% (n=110) patients in the VMP arm (P=0.0003).
  • Improved MRD-negativity (10-5) rate was observed in the D-VMP arm vs VMP arm across frailty subgroups (ITT Population)3:
    • For total non-frail patients, MRD-negativity (10-5) rate was 27.8% (n=52) in the D-VMP arm vs 6.4% (n=13) in the VMP arm (P<0.0001).
    • For frail patients, MRD-negativity (10-5) rate was 28.8% (n=47) in the D-VMP arm vs 7.9% (n=12) in the VMP arm (P<0.0001).
Safety

Most Common Grade 3/4 (≥10%) TEAEs in the Safety Population (ALCYONE)3
Event, n (%)
Total Non-Fraila (n=389)
Frail (n=311)
D-VMP (n=186)
VMP (n=203)
D-VMP (n=160)
VMP (n=151)
Total number of patients with grade 3/4 TEAE
150 (80.6)
151 (74.4)
127 (79.4)
123 (81.5)
Hematologic
   Neutropenia
73 (39.2)
86 (42.4)
66 (41.3)
52 (34.4)
   Thrombocytopenia
61 (32.8)
75 (36.9)
59 (36.9)
59 (39.1)
   Anemia
26 (14.0)
38 (18.7)
34 (21.3)
32 (21.2)
   Leukopenia
15 (8.1)
12 (5.9)
13 (8.1)
18 (11.9)
   Lymphopenia
13 (7.0)
9 (4.4)
14 (8.8)
13 (8.6)
Non-hematologic
   Infections
44 (23.7)
26 (12.8)
48 (30.0)
27 (17.9)
      Pneumonia
22 (11.8)
7 (3.4)
23 (14.4)
8 (5.3)
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; TEAE, treatment-emergent adverse events; VMP, bortezomib + melphalan + prednisone.
aTotal non-frail subgroup consists of fit and intermediate patients.

Most Common TEAEs Leading to Treatment Discontinuation (>1 Patient) and an Outcome of Death in the Safety Population (ALCYONE)3,12
Event, n (%)
Total Non-Fraila (n=389)
Frail (n=311)
D-VMP (n=186)
VMP (n=203)
D-VMP (n=160)
VMP (n=151)
Total number of patients with a TEAE leading to treatment discontinuation
10 (5.4)
14 (6.9)
14 (8.8)
19 (12.6)
Non-hematologic
   Fatigue
0
0
1 (0.6)
2 (1.3)
   Peripheral sensory neuropathy
0
2 (1.0)
0
4 (2.6)
   Infections
4 (2.2)
3 (1.5)
2 (1.3)
3 (2.0)
      Pneumonia
2 (1.1)
0
1 (0.6)
1 (0.7)
Total number of patients with a TEAE with an outcome of death
7 (3.8)
7 (3.4)
17 (10.6)
13 (8.6)
   Cardiac arrest
1 (0.5)
0
0
2 (1.3)
   Death
0
0
2 (1.3)
2 (1.3)
   Pneumonia
0
0
2 (1.3)
0
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; TEAE, treatment-emergent adverse event; VMP, bortezomib + melphalan + prednisone.
aTotal non-frail subgroup consists of fit and intermediate patients.

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
04 June 2025.

 

References

Show
1 Mateos M, Dimopoulos M, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378:518-528.  
2 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.  
3 Mateos M, Dimopoulos M, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of ALCYONE. Clin Lymphoma Myeloma Leuk. 2021;21:785-798.  
4 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.  
5 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-.  
6 Cavo M, San-Miguel J, Usmani SZ, et al. Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA. Blood. 2021;139(6):835-844.  
7 Knop S, Mateos MV, Dimopoulos MA, et al. Health-related quality of life in patients with newly diagnosed multiple myeloma ineligible for stem cell transplantation: results from the randomized phase III ALCYONE trial. Bmc Cancer. 2021;21(1):659.  
8 Burton T, Larholt K, Apgar E, et al. Long-term outcomes and health-related quality of life (HRQoL) by response status for bortezomib, melphalan, and prednisone (VMP) ¬± daratumumab (DARA) in ALCYONE. Poster presented at: Virtual 62ndAmerican Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020.  
9 San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood. 2022;139(4):492-501.  
10 Mateos M, Cavo M, Blade J, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020;395:132-141.  
11 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.  
12 Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE. Clin Lymphoma Myeloma Leukemia. 2021;21(11):785-798.