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DARZALEX FASPRO®

(daratumumab and hyaluronidase-fihj)

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DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)

Medical Information

DARZALEX FASPRO® (daratumumab and hyaluronidase)

Last Updated: 01/09/2026

Summary

  • Janssen does not recommend the use of DARZALEX for intravenous (IV) use or DARZALEX FASPRO for subcutaneous (SC) use in a manner that is inconsistent with the approved labeling.
  • No overall differences in effectiveness were observed based on age for DARZALEX or DARZALEX FASPRO. The incidence of serious adverse reactions was higher in older patients than in younger patients.1,2
  • MAIA is a phase 3 study evaluating the efficacy and safety of DARZALEX in combination with lenalidomide and dexamethasone (D-Rd) vs lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (NDMM).3
    • Facon et al (2025)4 reported the updated efficacy and safety results from the MAIA study at a median follow-up of 64.5 months. Median progression-free survival (PFS) improved with D-Rd vs Rd across subgroups of patients based on age (≥70 to <75 years: 61.9 vs 37.5 months; ≥75 years: 54.3 vs 31.4 months). No new safety concerns were observed with a longer follow-up. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 95.5% vs 95.0% of patients aged ≥75 years and in 92.3% vs 95.7% of patients aged ≥80 years from the D-Rd vs Rd arm, respectively. The rate of common grade 3/4 TEAEs in patients aged ≥75 years and those aged ≥80 years was similar to that in the overall study population.
  • ALCYONE is a phase 3 study evaluating the efficacy and safety DARZALEX in combination with bortezomib, melphalan, and prednisone (D-VMP) vs bortezomib, melphalan, and prednisone (VMP) in patients with NDMM ineligible for autologous stem cell transplant (ASCT).5
    • Mateos et al (2025)6 reported the final efficacy and safety analysis results of the ALCYONE study at a median follow-up of 86.7 months. The median age at randomization was 71 years (range, 40-93), with 30% of patients aged ≥75 years. For patients ≥75 years, the median PFS improved was not estimable (NE) for the D-VMP arm vs 20.4 months for the VMP arm (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.32-0.85). The most common grade 3 or 4 TEAEs in the D-VMP vs VMP group were neutropenia (40% vs 39%), thrombocytopenia (35% vs 38%), and anemia (18% vs 20%). 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.
  • AURIGA is a phase 3 study evaluating the conversion rate to minimal residual disease (MRD)-negativity after maintenance treatment with DARZALEX FASPRO in combination with lenalidomide (D-R) vs lenalidomide (R) alone in patients with NDMM who are anti-cluster of differentiation (CD) 38 naïve, have very good partial response or better (≥VGPR), and are MRD-positive following ASCT after standard of care induction and consolidation.7,8
    • Foster et al (2024)9 presented a post hoc analysis of the AURIGA study that evaluated clinically relevant subgroups in patients with NDMM at a median follow-up of 32.3 months. A subgroup analysis of MRD-negativity (10-5 sensitivity) conversion rates by 12 months of maintenance showed improvement for D-R vs R regardless of age. No additional safety concerns were observed in patients aged ≥65 years. DARZALEX FASPRO in combination with lenalidomide (D-R) maintenance did not increase grade 3/4 infection or cytopenia rates in patients ≥65 years of age.
  • PERSEUS is a phase 3 study evaluating the safety and efficacy of DARZALEX FASPRO in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) vs bortezomib, lenalidomide, and dexamethasone (VRd) induction and consolidation followed by maintenance with D-R in the D-VRd group or R alone in the VRd group in patients with NDMM eligible for ASCT.10 
    • Rodriguez-Otero et al (2024)11 presented MRD-negativity results from the PERSEUS study at a median follow-up of 47.5 months. For patients aged ≥65 years, the overall MRD-negativity rates were higher in the D-VRd vs VRd group at 10-5 sensitivity (67.0% [63/94] vs 49.4% [43/87]; odds ratio [OR], 2.08; 95% CI, 1.14-3.79) and 10-6 sensitivity (57.4% [54/94] vs 35.6% [37/87]; OR, 2.44; 95% CI, 1.34-4.44). The sustained (≥12 months) MRD-negativity rates were higher in the D-VRd vs VRd group at 10-5 sensitivity (53.2% [50/94] vs 31.0% [27/87]; OR, 2.53; 95% CI, 1.37-4.64) and 10-6 sensitivity (39.4% [37/94] vs 21.8% [19/87]; OR, 2.32; 95% CI, 1.21-4.48).
  • Rodriguez-Otero et al (2025)12 reported results from a post hoc, pooled analysis of data from the PERSEUS and GRIFFIN studies. These studies evaluated the efficacy and safety of DARZALEX FASPRO and DARZALEX in combination with VRd vs VRd in patients aged ≥65 years. At a median follow-up of 47.5 months and 49.6 months, the median PFS was not reached in the PERSEUS and GRIFFIN groups, respectively. The PFS HR for D-VRd vs VRd was 0.56 (95% CI, 0.31-1.01; P=0.05). A higher incidence of grade 3/4 infections was observed in the D-VRd vs VRd group in patients aged ≥65 years (36.3% vs 24.8%, respectively).
  • CANDOR is a phase 3 study evaluating the efficacy and safety of DARZALEX in combination with carfilzomib and dexamethasone (D-Kd) vs carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma (RRMM).13
    • Usmani et al (2023)14 reported the final efficacy and safety results at a median follow-up of ~50 months. The HR for median overall survival (OS) for the D-Kd arm in the prespecified subgroup of patients aged ≥65 years was 0.912 (95% CI, 0.603-1.381). The most common (≥15%) grade ≥3 TEAEs were thrombocytopenia (D-Kd, 24.7%; Kd, 16.3%), hypertension (D-Kd, 23.4%; Kd, 17.6%), pneumonia (D-Kd, 18.5%; Kd, 9.2%), and anemia (D-Kd, 17.5%; Kd, 16.3%).
  • APOLLO is a phase 3 study evaluating the efficacy and safety of DARZALEX in combination with pomalidomide and dexamethasone (D-Pd) vs pomalidomide and dexamethasone (Pd) in patients with RRMM who received ≥1 prior treatment with both lenalidomide and a proteasome inhibitor.15
    • Sonneveld et al (2021)16 presented updated efficacy and safety results of the APOLLO study, with a median duration of follow-up of 30.7 months. The median PFS for the D-Pd vs Pd arm in patients aged ≥65 years was 13.11 vs 7.23 months (HR, 0.60; 95% CI, 0.42-0.85) and that in patients aged <65 years was 8.34 vs 6.54 months (HR, 0.63; 95% CI, 0.41-0.96). The most common grade 3/4 TEAEs (≥5%) were neutropenia (D-Pd, 69.1%; Pd, 50.7%) and infections (D-Pd, 31.5%; Pd, 23.3%).
  • COLUMBA is a phase 3 study evaluating the efficacy, pharmacokinetics (PK), and infusion-related reactions (IRRs) of DARZALEX FASPRO vs DARZALEX in adults patients with heavily pre-treated RRMM.17
    • Usmani et al (2019)17 presented efficacy results for patients aged ≥75 years treated in the COLUMBA study. The overall response rate (ORR) in patients aged ≥75 years was 44.7% in the DARZALEX FASPRO arm vs 45.8% in the DARZALEX arm (relative risk [RR], 0.98; 95% CI, 0.63-1.48). The most common grade 3/4 TEAEs (>5%) were anemia (DARZALEX FASPRO, 14%; DARZALEX, 15%), thrombocytopenia (14% in both arms), and neutropenia (DARZALEX FASPRO, 13%; DARZALEX, 8%).
  • Other relevant literature has been identified in addition to the data summarized above and is listed in the References section for your information.18-25  

PRODUCT LABELING

COMPAny core data

  • No overall differences in effectiveness were observed based on age for DARZALEX or DARZALEX FASPRO. The incidence of serious adverse reactions was higher in older patients than in younger patients.1,2

DARZALEX:

  • Among patients with RRMM (n=1213), the most common serious adverse reactions that occurred more frequently in patients ≥65 years of age were pneumonia and sepsis. Among patients with NDMM who were ineligible for ASCT (n=710), the most common serious adverse reaction that occurred more frequently in patients ≥75 years of age was pneumonia.1
  • Based on population PK analyses in patients receiving monotherapy or various combinations therapies, age (range, 31-93 years) had no clinically important effect on the PK of daratumumab, and the exposure of daratumumab was similar between younger (aged <65 years: n=706) and older (aged ≥65 to <75 years: n=913; aged ≥75 years: n=369) patients.1

DARZALEX FASPRO:

  • Among patients with RRMM (n=2042), the most common serious adverse reactions that occurred more frequently in patients ≥65 years of age were pneumonia and sepsis. Among patients with NDMM who were ineligible for ASCT (n=777), the most common serious adverse reaction that occurred more frequently in patients ≥75 years of age was pneumonia.2
  • Among patients with NDMM who were eligible for ASCT (n=351), the most common serious adverse reaction that occurred more frequently in patients ≥65 years of age was pneumonia. Among patients with NDMM for whom ASCT was not planned as initial therapy or who were ineligible for a transplant (n=197), the most common serious adverse reaction that occurred more frequently in patients ≥65 years of age was pneumonia.2
  • Based on population PK analyses in patients (33-92 years) receiving monotherapy or various combination therapies, age had no statistically significant effect on the PK of daratumumab and hyaluronidase. No individualization is necessary for patients on the basis of age.2

Clinical Data – newly diagnosed multiple myeloma

Phase 3 Study of D-Rd in Patients with NDMM

MAIA (MMY3008; NCT02252172) is an international, phase 3, randomized, open-label, active-controlled, multicenter study in patients with NDMM not eligible for high-dose chemotherapy and ASCT.3 Facon et al (2025)4 reported the updated efficacy and safety results of this study at a median follow-up of 64.5 months (range, 0-77.6).

Study Design/Methods

  • Patients were randomized 1:1 to receive either of the following (28-day cycles)3:
    • D-Rd (n=368):
      • DARZALEX: 16 mg/kg IV every week (QW) on cycles 1-2, every 2 weeks (Q2W) on cycles 3-6, and every 4 weeks (Q4W) thereafter until disease progression.
      • Lenalidomide: 25 mg orally (PO) daily on days 1-21 until disease progression (10 mg daily if CrCl between 30-50 mL/min).
      • Dexamethasone: 40 mg PO weekly until PD (20 mg weekly in patients >75 years of age or with a body mass index [BMI] <18.5).
    • Rd (n=369): lenalidomide and dexamethasone as above.

Results

Patient Characteristics

Baseline Characteristics Based on Age Subgroups (MAIA)26
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)
Median age (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 PS, 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 stage, 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)
Cytogenetic profile, n (%)a
   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)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG, Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; ISS, International Staging System; Rd, lenalidomide + dexamethasone. aCytogenetic risk was assessed by FISH or karyotype testing; high risk defines as the presence of t(4;14), t(14;16), or del(17p).

Patient Disposition and Treatment Discontinuation According to Age Subgroups (MAIA)4,26
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

PFS and OS Based on Age Subgroups (MAIA)4
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.

Analysis of PFS in Prespecified Patient Subgroups (MAIA)a,26
Subgroup
D-Rd
Rd
HR (95% CI)b
n/N
Median PFS, Months
n/N
Median PFS, Months
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)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HR, hazard ratio; NE, not estimable; PFS, progression-free survival; Rd, lenalidomide + dexamethasone.
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.

Analysis of OS in Prespecified Patient Subgroups (MAIA)a,26
Subgroup
D-Rd
Rd
HR (95% CI)b
n/N
Median OS, Months
n/N
Median OS, Months
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)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HR, hazard ratio; NE, not estimable; OS, overall survival; Rd, lenalidomide + dexamethasone.
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.

Response Rates Based on Age Subgroups (MAIA)4
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.
Safety
  • No new safety concerns were observed with a longer follow-up.4
  • Grade 3/4 TEAEs occurred in 95.9% vs 88.8% of patients from the D-Rd vs Rd arm, respectively.4
    • Among patients aged ≥75 years, grade 3/4 TEAEs occurred in 95.5% vs 95.0% of patients from the D-Rd vs Rd arm, respectively.
    • Among patients aged ≥80 years, grade 3/4 TEAEs occurred in 92.3% vs 95.7% of patients from the D-Rd vs Rd arm, respectively.
    • The rates of common grade 3/4 TEAEs in patients aged ≥75 years and those aged ≥80 years were similar to those in the overall study population.
    • 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). A summary of the most common TEAEs is presented in Table: Most Common Any-Grade or Grade 3/4 TEAEs Among Patients Aged ≥75 Years and ≥80 Years in the Safety Population (MAIA).26
  • Grade 3/4 infections occurred in 42.6% vs 29.6% of patients from the D-Rd vs Rd arm, respectively.4
  • 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).4
    • 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%).4
    • 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.4
    • 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 Among Patients Aged ≥75 Years and ≥80 Years in the Safety Population (MAIA)a,26
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.

Phase 3 Study of D-VMP in Transplant-Ineligible Patients with NDMM

ALCYONE (MMY3007; NCT02195479) is a phase 3, multicenter, randomized, open-label, active-controlled study which evaluated the safety and efficacy of D-VMP compared with VMP alone for the treatment of NDMM in patients who were ineligible for high-dose chemotherapy with ASCT.5 Mateos et al (2025)6 reported the final efficacy and safety analysis results of the ALCYONE study at a median follow-up of 86.7 months.

Study Design/Methods

  • Patients were randomized 1:1 to receive D-VMP or VMP.5
  • In both treatment groups, patients received up to nine 6-week cycles of subcutaneous bortezomib (1.3 mg/m2 of body surface area, twice per week on weeks 1, 2, 4, and 5 of cycle 1 and QW on weeks 1, 2, 4, and 5 of cycles 2-9), oral melphalan (9 mg/m², once daily on days 1-4 of each cycle), and prednisone (60 mg/m², once daily on days 1-4 of each cycle).5
  • In the D-VMP group, patients received DARZALEX at a dose of 16 mg/kg IV QW during cycle 1; once every 3 weeks (Q3W) during cycles 2-9; and Q4W thereafter until disease progression, unacceptably toxicity, or the end of study.5

Results

Patient Characteristics and Disposition
  • Key baseline characteristics are summarized in Table: Baseline Characteristics in the ITT Population (ALCYONE).27
  • At final analysis clinical cutoff date of May 31, 2023, the median duration of treatment in the D-VMP vs VMP groups was 33.0 months (interquartile range [IQR], 14.5-77.3) vs 12.0 months (IQR, 7.2-12.0), respectively.6

Baseline Characteristics in the ITT Population (ALCYONE)a,27
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)
Abbreviations: D-VMP, DARZALEX + bortezomib + melphalan + prednisone; ITT, intention-to-treat; VMP, bortezomib + melphalan + prednisone.
aThe ITT population was defined as all patients who were randomized.
Efficacy

OS in Prespecified Subgroups in the ITT Population (ALCYONE)6 
Subgroup
D-VMP
VMP
HR (95% CI)
Events/Patients
n/N
Median
(95% CI), Months
Events/Patients
sn/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)
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)
Abbreviations: CI, confidence interval; D-VMP, DARZALEX + bortezomib + melphalan + prednisone; HR, hazard ratio; ITT, intention-to-treat; NE, not estimable; OS, overall survival; VMP, bortezomib + melphalan + prednisone.
Safety
  • 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).6
    • Grade 3 or 4 TEAEs occurred in 83% of patients receiving D-VMP and 77% of patients receiving VMP.
    • The most common grade 3 or 4 infection in both treatment groups was pneumonia (D-VMP, 16%; VMP, 5%).
    • 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.
      • In the D-VMP group, IRRs of any grade, grade 3, and serious TEAEs were reported in <1% of patients.27
      • No IRRs of any grade were reported in the VMP group.27
    • The D-VMP group experienced a higher rate of serious TEAEs compared with the VMP group (21% vs 16%). The most common serious TEAE observed in D-VMP vs VMP group was pneumonia (5% vs 2%, respectively).
  • The incidence of second primary malignancies (SPMs) in the D-VMP vs VMP group was 8% vs 6%, respectively.6
    • The most frequently reported SPM 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).6,27
  • Death due to adverse events was reported in 10% vs 6% of patients in the D-VMP vs VMP group, respectively.6

Summary of the Most Common TEAEs (ALCYONE)6
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
Nonhematologic 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.

Phase 3 Study of D-R Maintenance in Patients with NDMM

AURIGA (MMY3021; NCT03901963) is an ongoing, open-label, active-controlled, multicenter, randomized, phase 3 study evaluating the conversion rate to MRD-negativity after maintenance treatment with DR vs R alone in patients with NDMM who are MRD positive after ASCT.7,8 Foster et al (2024)9 presented a post hoc analysis of the phase 3 AURIGA study that evaluated clinically relevant subgroups in patients with NDMM at a median follow-up of 32.3 months.

Study Design/Methods

  • Patients underwent 1:1 randomization to receive D-R or R alone across 28-day cycles.7
    • DARZALEX FASPRO: 1800 mg SC QW in cycles 1-2, Q2W in cycles 3-6, Q4W in cycles 7+.
    • Lenalidomide: 10 mg PO once a day on days 1-28.
  • The treatment regimen continued until unacceptable toxicity, disease progression, consent withdrawal, or for a maximum of 36 cycles.7
  • The clinically relevant subgroups included elderly and Black patients; patients with high-risk disease per International Staging System (ISS) disease staging; and patients with a high cytogenetic risk per standard, revised, and IMS 2024 high-risk criteria.9

Results

Demographics and Disease Characteristics
  • A total of 200 patients were randomized into the D-R maintenance (n=99) vs R alone maintenance (n=101) groups.9 
  • The median follow-up was 32.3 months.9 
  • Demographics and disease characteristics of the intention-to-treat (ITT) population are presented in Table: Baseline Characteristics of the ITT Population (AURIGA).9
  • The median duration of therapy was 25.0 months (D-R, 30.5 months; lenalidomide, 23.5 months) for patients aged <65 years and 24.4 months (D-R, 32.7 months; lenalidomide, 19.2 months) for patients aged ≥65 years.9

Baseline Characteristics of the ITT Population (AURIGA)9 
D-R
(n=99)
R
(n=101)
Age, n (%)
   <65 years
61 (61.6)
61 (60.4)
   ≥65 years
38 (38.4)
40 (39.6)
Abbreviations: D-R, DARZALEX FASPRO + lenalidomide; ITT, intention-to-treat; R, lenalidomide.
Efficacy

Subgroup Analysis of MRD-negativity (10-5 Sensitivity) Conversion Ratea from Baseline to 12 Months of Maintenance Treatment9 
Subgroup, n/N (%)
D-R
R
ORb (95% CI)
ITTc
50/99 (50.5)
19/101 (18.8)
4.51 (2.37-8.57)
Age
   <65 years
30/61 (49.2)
12/61 (19.7)
3.95 (1.76-8.85)
   ≥65 years
20/38 (52.6)
7/40 (17.5)
5.24 (1.86-14.74)
Abbreviations: CI, confidence interval; D-R, DARZALEX FASPRO + lenalidomide; IMWG, International Myeloma Working Group; ITT, intention-to-treat; MRD, minimal residual disease; NGS, nextgeneration sequencing; OR, odds ratio; R, lenalidomide.
aDefined as the proportion of patients who achieved MRD-negative status (at 10-5) by NGS by 12 months after maintenance treatment and prior to progressive disease or subsequent antimyeloma therapy.
bMantel-Haenszel estimate of the common OR for stratified tables is used for ITT; Mantel-Haenszel estimate of the common OR for unstratified tables is used for subgroups. An OR >1 indicates an advantage for D-R.cITT analysis set is defined as all patients who were randomized to treatment.
Safety

Safety Results for Patients With ≥1 TEAE Based on Age (AURIGA)9 
Patients With ≥1 TEAE, n (%)
D-R
R
<65 Years
(n=59)
≥65 Years
(n=37)
<65 Years
(n=58)
≥65 Years
(n=40)
Grade 3/4 TEAEs
45 (76.3)
26 (70.3)
37 (63.8)
29 (72.5)
Most commona
      Neutropeniab
26 (44.1)
19 (51.4)
25 (43.1)
16 (40.0)
      Lymphopenia
7 (11.9)
3 (8.1)
3 (5.2)
2 (5.0)
      Hypertension
6 (10.2)
1 (2.7)
3 (5.2)
1 (2.5)
      Leukopenia
6 (10.2)
3 (8.1)
2 (3.4)
4 (10.0)
      Hypokalemia
4 (6.8)
3 (8.1)
2 (3.4)
4 (10.0)
      Pneumonia
1 (1.7)
4 (10.8)
1 (1.7)
3 (7.5)
Grade 3/4 cytopenias
31 (52.5)
21 (56.8)
27 (46.6)
19 (47.5)
Grade 3/4 infections
11 (18.6)
7 (18.9)
6 (10.3)
7 (17.5)
Serious TEAEs
14 (23.7)
15 (40.5)
7 (12.1)
15 (37.5)
COVID-19 events
   Any grade
19 (32.2)
9 (24.3)
22 (37.9)
7 (17.5)
   Grade 3/4
1 (1.7)
0 (0.0)
3 (5.2)
0 (0.0)
TEAEs leading to discontinuation of any treatment componentc
7 (11.9)
7 (18.9)
4 (6.9)
4 (10.0)
Death due to TEAEs
0 (0.0)
2 (5.4)
0 (0.0)
1 (2.5)
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; D-R, DARZALEX FASPRO + lenalidomide; R, lenalidomide; TEAE, treatment-emergent adverse event.
aOccurring in ≥10% of patients in either treatment group in either age category.
bPreferred term grouping.
cIncludes those who had AEs with action taken as drug withdrawn to ≥1 component of study treatment on the “AE” complete report form page.

Post hoc Analysis of Patients Aged ≥65 Years from the PERSEUS and GRIFFIN Studies

Rodriguez-Otero et al (2025)12 presented results from a post hoc, pooled analysis of data from the PERSEUS and GRIFFIN studies that evaluated the efficacy and safety of DARZALEX FASPRO or DARZALEX, respectively, in combination with VRd vs VRd in patients aged ≥65 years.

Results

Patient Characteristics
  • Patients aged ≥65 years represented 25.5% of patients in the PERSEUS study (D-VRd, 94 of 355 patients vs VRd, 87 of 354 patients) and 27.1% of patients in the GRIFFIN study (D-VRd, 28 of 104 patients vs VRd, 28 of 103 patients).12
  • The baseline demographic and disease characteristics are summarized in Table: Baseline Characteristics in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN ITT Population.12
  • The median duration of treatment for patients aged ≥65 years was 37.4 months (range, 0.5-52.5) and 32.6 months (range, 0.1-53.0) in the D-VRd and VRd groups, respectively.12
  • The median number of treatment cycles received in the D-VRd vs VRd group were 33.5 vs 31.0 cycles.12
  • Cycle delays were reported in the D-VRd vs VRd group for 82.5% vs 75.4% of patients, respectively.12
  • Treatment discontinuation rates in the D-VRd vs VRd group were higher for lenalidomide (23.3% vs 17.5%, respectively) but were comparable between the D-VRd vs VRd group for bortezomib (12.5% vs 12.3%, respectively) and dexamethasone (3.3% vs 3.5%, respectively).12
  • The discontinuation rate of DARZALEX FASPRO/DARZALEX in the D-VRd group was 2.5%.12

Baseline Characteristics in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN ITT Populationa,12
Characteristic
D-VRd
(n=122)
VRd
(n=115)
Median age (range), years
67 (65-70)
67 (65-70)
Sex
   Female, n (%)
46 (37.7)
48 (41.7)
   Male, n (%)
76 (62.3)
67 (58.3)
Race, n (%)
   White
110 (90.2)
106 (92.2)
   Asian
4 (3.3)
1 (0.9)
   Black
2 (1.6)
3 (2.6)
   American Indian/Alaska Native
1 (0.8)
0
   Native Hawaiian/Pacific Islander
1 (0.8)
0
   Multiple/unknown/not reported
4 (3.3)
5 (4.3)
ECOG PS score, n/N (%)
   0
66/122 (54.1)
66/114 (57.9)
   1
47/122 (38.5)
40/114 (35.1)
   2
9/122 (7.4)
8/114 (7.0)
   3
0
0
ISS disease stageb, n (%)
   I
51 (41.8)
39 (33.9)
   II
32 (26.2)
33 (28.7)
   III
11 (9.0)
15 (13.0)
Type of measurable diseasec, n (%)
   Serum
96 (78.7)
100 (87.0)
      IgG
67 (54.9)
65 (56.5)
      IgA
24 (19.7)
28 (24.3)
      Otherd
5 (4.1)
7 (6.1)
   Urine only
13 (10.7)
9 (7.8)
   Serum FLC only
12 (9.8)
6 (5.2)
   Not evaluablee
1 (0.8)
0
Cytogenetic riskf, n/N (%)
   Standard risk
88/119 (73.9)
91/114 (79.8)
   High risk
27/119 (22.7)
22/114 (19.3)
      del(17p)
17/119 (14.3)
12/114 (10.5)
      t(4;14)
10/119 (8.4)
7/114 (6.1)
      t(14;16)
2/119 (1.7)
5/114 (4.4)
      Indeterminate
4/119 (3.4)
1/114 (0.9)
Abbreviations: D-VRd, DARZALEX FASPRO/DARZALEX + bortezomib, lenalidomide, and dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FLC, free-light chain; IgA/IgD/IgE/IgG/IgM, immunoglobulin A/D/E/G/M; ISS, International Staging System; ITT, intent-to-treat; VRd, bortezomib, lenalidomide, and dexamethasone.aThe pooled ITT population included all patients aged ≥65 years who were randomized in PERSEUS or GRIFFIN.
bISS staging is derived based on the combination of serum β2-microglobulin and albumin.
cIncludes patients without measurable disease in serum and urine.
dIncludes patients with IgD, IgM, IgE, and biclonal disease.eOne patient with no evaluable measurable disease.
fHigh risk was defined as ≥1 of the following cytogenetic abnormalities: del(17p), t(4;14), and/or t(14;16) by fluorescence in situ hybridization. Standard risk was defined by the absence of these cytogenetic abnormalities.
Transplant Characteristics
  • Among patients aged ≥65 years who received ≥1 dose of the study treatment, 93.3% (112/120) vs 84.2% (96/114) patients in the D-VRd vs VRd group, proceeded for stem cell mobilization.12
    • The median number of CD34+ cells collected was sufficient for transplant in both the treatment groups.
    • Two patients from the D-VRd group vs 1 patient from the VRd group had <2×106/kg CD34+ stem cells collected.
  • The proportions of patients who proceeded to transplant were comparable between the treatment groups (D-VRd, 86.7% vs VRd, 82.5%).12
    • The median time to engraftment was 14 (range, 0-33) days vs 13 (range, 1-48) days in the D-VRd vs VRD groups, respectively.
  • The stem cell mobilization and transplant outcomes are summarized in Table: Stem Cell Mobilization and Transplant Outcomes in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN Safety Population.12

Stem Cell Mobilization and Transplant Outcomes in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN Safety Populationa,12
Characteristic
D-VRd
(n=120)
VRd
(n=114)
Patients proceeded to stem cell mobilization, n (%)
112 (93.3)
96 (84.2)
Mobilization medication/therapy used, n (%)
   N
112
96
   G-CSFb
110 (98.2)
91 (94.8)
   Cyclophosphamide
71 (63.4)
51 (53.1)
   Plerixafor
59 (52.7)
32 (33.3)
   Chemotherapy
2 (1.8)
0 (0)
   Other
1 (0.9)
2 (2.1)
Patients with stem cells collected, n (%)
108 (90.0)
95 (83.3)
Total number of CD34+ stem cells collected
   Median (range),×106/kg
4.22 (1.80-13.50)
5.76 (1.12-49.50)
   <2×106/kg, n (%)
2 (1.9)
1 (1.1)
   2 to <5×106/kg, n (%)
68 (63.0)
35 (36.8)
   ≥5×106/kg, n (%)
38 (35.2)
59 (62.1)
Patients who completed stem cell conditioning therapy, n (%)
104 (86.7)
94 (82.5)
Total dose of melphalan conditioning therapy
   N
102
94
   Median (range), mg/m2
193 (59-385)
192 (52-371)
Patients who proceeded to ASCT, n (%)
104 (86.7)
94 (82.5)
Time to achieve ANC ≥0.5×109/L, post-transplant
   N
103
93
   Median (range), days
13 (0-28)
12 (0-34)
Time to achieve platelets ≥20×109/L post-transplant without transfusionc
   N
103
93
   Median (range), days
13 (0-33)
12 (1-48)
Time to engraftmentc,d
N
103
93
Median (range), days
14 (0-33)
13 (1-48)
Abbreviations: ANC, absolute neutrophil count; ASCT, autologous stem cell transplant; CD, cluster of differentiation; D-VRd, DARZALEX FASPRO/DARZALEX + bortezomib, lenalidomide, and dexamethasone; G-CSF, granulocyte colony-stimulating factor; VRd, bortezomib, lenalidomide, and dexamethasone.
aPooled safety population included all patients aged ≥65 years who were randomized in PERSEUS or GRIFFIN and received ≥1 dose of study treatment.
bIncluded standardized medications of filgrastim, lenograstim, and G-CSF.
cNumber of days from the transplant date, excluding patients whose counts did not reach nadir below the set threshold.dThe date of engraftment after transplant was defined as the latest date of ANC ≥0.5×109/L and platelet count ≥20×109/L. Patients with hematopoietic reconstitution were included.
Efficacy

Response Rates, Overall and Sustained MRD-Negativity Rates in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN ITT Populationa,12
Parameter
D-VRd
(n=122)
VRd
(n=115)
OR
(95% CI)b
P Valuec
n (%)
95% CI
n (%)
95% CI
≥CR
101
(82.8)
74.9-89.0
77
(67.0)
57.6-75.4
2.37
(1.28-4.39)
0.005
≥VGPR
114
(93.4)
87.5-97.1
99
(86.1)
78.4-91.8
2.47
(1.03-5.92)
0.04
ORRd
116
(95.1)
89.6-98.2
110
(95.7)
90.1-98.6
0.86
(0.25-2.96)
0.81
Best response
   sCR
72 (59.0)
49.7-67.8
57 (49.6)
40.1-59.0
1.49
(0.88-2.53)
0.14
   CR
29 (23.8)
16.5-32.3
20 (17.4)
11.0-25.6
-
-
   VGPR
13 (10.7)
5.8-17.5
22 (19.1)
12.4-27.5
-
-
   PR
2 (1.6)
0.2-5.8
11 (9.6)
4.9-16.5
-
-
   SD
3 (2.5)
0.5-7.0
2 (1.7)
0.2-6.1
-
-
   PD
0
NE-NE
0
NE-NE
-
   NE
3 (2.5)
0.5-7.0
3 (2.6)
0.5-7.4
-
Overall MRD-negativity (10-5), %
81 (66.4)
-
48 (41.7)
-
2.75
(1.61-4.71)
0.0002
MRD-negativity (10-5) at the end of consolidation, %
60 (49.2)
-
34 (29.6)
-
2.23
(1.31-3.80)
0.003
Sustained MRD-negativity (10-5) (≥12 months), %
64 (52.5)
-
30 (26.1)
-
3.2
(1.83-5.58)
<0.0001
Abbreviations: CI, confidence interval; CR, complete response; D-VRd, DARZALEX FASPRO/DARZALEX + bortezomib + lenalidomide + dexamethasone; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; ORR, overall response rate; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response; VRd, bortezomib + lenalidomide + dexamethasone. aPooled ITT population included all patients aged ≥65 years who were randomized in PERSEUS or GRIFFIN.bMantel-Haenszel estimates of the common ORs for stratified tables were used. The stratification factors were ISS disease stage (I vs II vs III) and cytogenetic risk (high risk vs standard/unknown risk).cP value from the stratified Cochran-Mantel-Haenszel chi-square test.
dORR was defined as sCR + CR + VGPR + PR.
Safety
  • The incidence of grade 3/4 TEAEs in the D-VRd vs VRd group among patients aged ≥65 years was 94.2% vs 86.8%, respectively.12
    • The incidence of serious TEAEs in the D-VRd vs VRd group among patients aged ≥65 years was 67.5% vs 52.6%, respectively.
  • A higher incidence of grade 3/4 infections of 36.3% vs 24.8% was observed in patients aged ≥65 years in the D-VRd vs VRd group, respectively.12
  • The percentage of patients with TEAEs that resulted in the discontinuation of ≥1 study drug in the D-VRd vs VRd group was 40.8% vs 45.6%, respectively, in patients aged ≥65 years. The summary of the most common TEAEs is presented in Table: Most Common TEAEs in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN Safety Population.12
  • Treatment discontinuation was mostly due to peripheral sensory neuropathy: D-VRd, 12.5%; VRd, 13.2%.12

Most Common TEAEs in Patients Aged ≥65 Years in the Pooled PERSEUS/GRIFFIN Safety Populationa,b,12
TEAEs, n (%)
D-VRd
(n=120)
VRd
(n=114)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Hematologic TEAEs
   Neutropeniac
80 (66.7)
71 (59.2)
61 (53.5)
49 (43.0)
   Thrombocytopenia
66 (55.0)
46 (38.3)
44 (38.6)
22 (19.3)
   Anemia
33 (27.5)
8 (6.7)
29 (25.4)
7 (6.1)
Nonhematologic TEAEs
   Diarrhea
71 (59.2)
17 (14.2)
66 (57.9)
12 (10.5)
   Peripheral sensory neuropathy
69 (57.5)
7 (5.8)
55 (48.2)
7 (6.1)
   Constipation
58 (48.3)
3 (2.5)
47 (41.2)
1 (0.9)
   Pyrexia
45 (37.5)
3 (2.5)
37 (32.5)
2 (1.8)
   Fatigue
44 (36.7)
6 (5.0)
39 (34.2)
7 (6.1)
   Upper respiratory tract infection
43 (35.8)
1 (0.8)
40 (35.1)
2 (1.8)
   Edema peripheral
43 (35.8)
4 (3.3)
35 (30.7)
3 (2.6)
   Cough
43 (35.8)
1 (0.8)
22 (19.3)
0 (0.0)
   Back pain
39 (32.5)
1 (0.8)
22 (19.3)
0 (0.0)
   Nausea
38 (31.7)
2 (1.7)
26 (22.8)
1 (0.9)
   Rash
33 (27.5)
4 (3.3)
24 (21.1)
8 (7.0)
   Arthralgia
30 (25.0)
0 (0.0)
25 (21.9)
1 (0.9)
   Insomnia
30 (25.0)
4 (3.3)
21 (18.4)
3 (2.6)
   Asthenia
26 (21.7)
2 (1.7)
31 (27.2)
2 (1.8)
   COVID-19
26 (21.7)
1 (0.8)
17 (14.9)
0 (0.0)
   Muscle spasms
24 (20.0)
2 (1.7)
27 (23.7)
2 (1.8)
   Bronchitis
24 (20.0)
2 (1.7)
13 (11.4)
1 (0.9)
   Pneumonia
23 (19.2)
13 (10.8)
17 (14.9)
7 (6.1)
   Hypokalemia
23 (19.2)
5 (4.2)
26 (22.8)
7 (6.1)
Abbreviations: D-VRd, DARZALEX FASPRO/DARZALEX + bortezomib + lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; VRd, bortezomib + lenalidomide + dexamethasone. aTEAEs of any grade that occurred in ≥20% of patients aged ≥65 years in either treatment group, or grade 3/4 TEAEs that occurred in ≥10% of patients aged ≥65 years in either treatment group. bThe pooled safety population includes all patients who were randomized in GRIFFIN or PERSEUS and received ≥1 dose of study treatment. cNeutropenia as a grouped term that included the preferred terms neutropenia and febrile neutropenia.

CLinical data – relapsed/refractory multiple myeloma

Phase 3 Study of D-Kd in Patients with RRMM

CANDOR (NCT03158688) is a randomized, open-label, multicenter, phase 3 study evaluating the efficacy and safety of D-Kd vs Kd in patients with RRMM who received 1-3 prior lines of therapy.13 Usmani et al (2023)14 reported the updated efficacy and safety results after a median follow-up of approximately 50 months.

Study Design/Methods

  • Patients were randomized 2:1 to receive either of the following as 28-day cycles until disease progression13:
    • D-Kd:
      • DARZALEX 16 mg/kg IV QW cycles 1-2 (first dose split over days 1 and 2 [8 mg/kg each] of cycle 1); Q2W cycles 3-6; Q4W thereafter.
      • Carfilzomib IV on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m2 on days 1, 2 of cycle 1, 56 mg/m2 thereafter).
      • Dexamethasone 40 mg PO or IV weekly (or 20 mg if ≥75 years starting on the second week).
    • Kd: Carfilzomib and dexamethasone as above.

Results

Patient Characteristics

Key Baseline Characteristics (CANDOR)14
Characteristic 
D-Kd
(n=312)
Kd
(n=154)
Median age (range), years
64.0 (57-70)
64.5 (59-71)
   ≤64, n (%)
163 (52)
77 (50)
   65-74, n (%)
121 (39)
55 (38)
   ≥75, n (%)
28 (9)
22 (14)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone.
Efficacy

OS in Prespecified Age Subgroups (CANDOR)14
Age at Baseline, Years
D-Kd (n=312)
Kd (n=154)
Hazard Ratio (95% CI)
Events/
Participants
Median OS (95% CI), Months
Events/
Participants
Median OS (95% CI), Months
<65
75/163
NE (43.2-NE)
44/77
41.5 (32.6-NE)
0.714
(0.487-1.045)
≥65
73/149
48.8 (42.4-NE)
36/77
50.3 (30.8-NE)
0.912
(0.603-1.381)
Abbreviations: CI, confidence interval; D-Kd, DARZALEX, carfilzomib, and dexamethasone; Kd, carfilzomib and dexamethasone; NE, not estimable; OS, overall survival.
Safety
  • Updated safety data was consistent with previously reported results, and no new safety signals were identified with the longer follow-up. In the D-Kd vs Kd arms14:
    • Grade ≥3 TEAEs occurred in 273 (88.6%) vs 120 (78.4%) patients.
    • Serious TEAEs occurred in 211 (68.5%) vs 80 (52.3%) patients.
    • Adverse events (AEs) leading to treatment discontinuation occurred in 105 (34.1%) vs 41 (26.8%) patients.
  • Fatal TEAEs in patients ≥65 years and <65 years are summarized in Table: Fatal TEAEs (CANDOR).28

Fatal TEAEs (CANDOR)a,28
Parameter
D-Kd
Kd
Fatal TEAEs, n (%)
35 (11.4)
9 (5.9)
   Age ≥65 years
25 (17.4)
3 (3.9)
   Age <65 years
10 (6.3)
6 (8.0)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event.
aExcludes fatal TEAE of plasma cell myeloma.

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 18 December 2025.

 

References

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26 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.  
27 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.  
28 Usmani S, Quach H, Mateos M, et al. Supplement to: Final analysis of carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone in the CANDOR Study. Blood Adv. 2023;7(14):3739-3748.