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DARZALEX FASPRO®

(daratumumab and hyaluronidase-fihj)

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DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)
Medical Information

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

Last Updated: 06/03/2026

Summary

  • Johnson & Johnson does not recommend the use of DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
  • CEPHEUS is a phase 3 study evaluating the efficacy and safety of DARZALEX FASPRO in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) vs bortezomib, lenalidomide, and dexamethasone (VRd) alone in patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible (TIE) or for whom transplant is not planned as initial therapy (transplant deferred).1
    • Usmani et al (2026)2 presented the final efficacy and safety results of the TIE population of the CEPHEUS study at a median follow-up of 76 months. Overall minimal residual disease (MRD) negativity (10-5) in patients with complete response or better (≥CR) was achieved in 61.1% of patients in the D-VRd arm vs 40.0% of patients in the VRd arm (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.47-3.77). Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 93.8% of patients in the D-VRd arm vs 88.7% in the VRd arm.
  • PLEIADES was a phase 2 study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with various treatment regimens in patients with multiple myeloma (MM), including DARZALEX FASPRO + bortezomib, melphalan, and prednisone (D-VMP) in NDMM.3
    • Moreau et al (2020)3 presented the updated safety and efficacy results of the PLEIADES study at a median follow-up of 25.2 months. Among patients with NDMM who received D-VMP, the overall response rate (ORR) was 89.6%, and the MRD-negativity rate was 25.4%. Grade 3/4 TEAEs were reported in 78% of patients; the most common (≥20%) being thrombocytopenia (45%), neutropenia (37%), and lymphopenia (22%).
  • IFM2017-03 was a phase 3 study assessing the safety and efficacy of DARZALEX FASPRO in combination with lenalidomide and dexamethasone (D-R) vs lenalidomide and dexamethasone (Rd) in elderly frail patients with NDMM who were not eligible for high-dose chemotherapy and autologous stem cell transplant (ASCT).4 
    • Manier et al (2025)4 reported results of the IFM2017-03 study. At a median follow-up of 46.3 months, disease progression or death occurred in 162 patients (D-R, 46%; Rd, 73%). The median progression-free survival (PFS) in the D-R vs Rd group was 53.4 months (95% CI, 35.3-not reached [NR]) vs 22.5 months (95% CI, 16.5-39), respectively (hazard ratio [HR], 0.51; 95% CI, 0.37-0.7; P<0.0001). Grade ≥3 adverse events (AEs) were reported in 178 patients (89%) in the D-R group and 75 patients (79%) in the Rd group.

CLINICAL DATA

Phase 3 Study of DARZALEX FASPRO in Combination VRd in TIE NDMM

CEPHEUS (MMY3019; NCT03652064) is a phase 3, randomized, open-label, multicenter study evaluating the efficacy and safety of D-VRd vs VRd in patients with NDMM who are transplant ineligible or for whom transplant is not planned as initial therapy (transplant deferred).1

Final Analysis of TIE Patients in the CEPHEUS Study

Usmani et al (2026)2 reported the final analysis of TIE patients in the CEPHEUS study at a median follow-up of 76 months.

Results

Patient Characteristics
  • Of the 395 patients enrolled in the study, 298 were ineligible for transplant (D-VRd, n=144; VRd, n=145).2
  • The baseline characteristics of TIE patients are summarized in Table: Baseline Characteristics of TIE Population.5

Baseline Characteristics of TIE Population5
Characteristic
D-VRd (n=144)
VRd (n=145)
Median age (range), years
72 (58-79)
72 (51-80)
   <70 years, n (%)
35 (24.3)
35 (24.1)
   70 to <75 years, n (%)
68 (47.2)
65 (44.8)
   ≥75 years, n (%)
41 (28.5)
45 (31.0)
Male, n (%)
65 (45.1)
82 (56.6)
ECOG PSa, n (%)
   0
52 (36.1)
57 (39.3)
   1
75 (52.1)
78 (53.8)
   2
17 (11.8)
10 (6.9)
IMWG frailty scoreb, n (%)
   0 (fit)
82 (56.9)
88 (60.7)
   1 (intermediate fitness)
62 (43.1)
57 (39.3)
IFM frailty score, n (%)
   Nonfrail (0-1)
96 (66.7)
110 (75.9)
   Frail (≥2)
48 (33.3)
35 (24.1)
Type of myeloma by immunofixation or serum FLC assay, n (%)
   IgG
92 (63.9)
78 (53.8)
   IgA
26 (18.1)
42 (29.0)
   IgD
2 (1.4)
2 (1.4)
   Light chain
20 (13.9)
19 (13.1)
   Biclonal
4 (2.8)
3 (2.1)
   Unknown
0
1 (0.7)
Extramedullary plasmacytomas, n (%)
9 (6.3)
12 (8.3)
ISS disease stagec, n (%)
   I
50 (34.7)
48 (33.1)
   II
54 (37.5)
57 (39.3)
   III
40 (27.8)
40 (27.6)
Cytogenetic risk profiled, n (%)
   Standard
105 (72.9)
111 (76.6)
   High
20 (13.9)
18 (12.4)
   Unevaluable or missing
19 (13.2)
16 (11.0)
Abbreviations: D-VRd, DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FLC, free light chain; IFM, Intergroupe Francophone du Myelome; Ig, immunoglobulin; IMWG, International Myeloma Working group; ISS, International Staging System; TIE, transplant-ineligible; VRd, bortezomib + lenalidomide + dexamethasone.
aECOG PS is scored on a scale of 0-5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bTotal additive frailty is scored on a scale of 0-5 based on age, comorbidities, and cognitive and physical conditions, with 0 indicating fit, 1 indicating intermediate fitness, and ≥2 indicating frail, per the Myeloma Geriatric Assessment score (http://www.myelomafrailtyscorecalculator.net/).
cBased on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease.
dBased on fluorescence in situ hybridization; high risk was defined as the presence of del(17p), t(4;14), and/or t(14;16).
Efficacy
  • Overall MRD negativity rates (10-5) in patients with ≥CR was higher in the D-VRd arm vs the VRd arm, with 61.1% of patients in the D-VRd arm achieving overall MRD negativity vs 40.0% in the VRd arm (OR, 2.35; 95% CI, 1.47-3.77). See Table: Summary of MRD Negativity Rates (TIE Subgroup).2
    • Sustained MRD negativity rate at ≥12 and ≥24 months was higher in the D-VRd arm vs the V-Rd arm.

Summary of MRD Negativity Rates (TIE Subgroup)2
Parameter, n (%)
D-VRd
(n=144)
VRd
(N=145)
OR (95% CI)
P-value
Overall MRD negativity (≥CR) ratea
   10-5 threshold
61.1
40.0
2.35 (1.47-3.77)
0.0004
   10-6 threshold
46.5
27.6
2.27 (1.39-3.71)
0.0010
Sustained MRD negativity (≥CR) rate ≥12 monthsb
   10-5 threshold
49.3
29.0
2.40 (1.47-3.91)
0.0005
   10-6 threshold
37.5
16.6
3.01 (1.73-5.24)
<0.0001
Sustained MRD negativity (≥CR) rate ≥24 monthsb
   10-5 threshold
44.4
23.4
2.62 (1.58-4.36)
0.0002
   10-6 threshold
30.6
15.2
2.45 (1.38-4.37)
0.0020
Abbreviations: CI, confidence interval, CR, complete response; D-VRd, DARZLEX FASPRO + bortezomib + lenalidomide + dexamethasone; MRD, minimal residual disease; OR, odds ratio; TIE, transplant ineligible; VRd, bortezomib + lenalidomide + dexamethasone.
aThe proportion of patients who achieved MRD negativity and ≥CR.
bSustained MRD negativity was defined as 2 consecutive MRD negative reads ≥12 months (±1) or 24 months (±3) apart with no MRD-positive result in between.

Prespecified Subgroup Analysis of MRD Negativity (TIE Subgroup)2
Subgroup
D-VRd
VRd
OR (95% CI)
MRD negativity (≥CR; 10-5), n/N (%)
Sex
   Male
43/65 (66.2)
29/82 (35.4)
3.57 (1.80-7.08)
   Female
45/79 (57.0)
29/63 (46.0)
1.55 (0.80-3.02)
Age
   <70 years
26/35 (74.3)
15/35 (42.9)
3.85 (1.40-10.59)
   ≥70 years
62/109 (56.9)
43/110 (39.1)
2.06 (1.20-3.52)
Region
   Europe
55/96 (57.3)
37/90 (41.1)
1.92 (1.07-3.44)
   North America
20/31 (64.5)
12/28 (42.9)
2.42 (0.85-6.92)
   Other
13/17 (76.5)
9/27 (33.3)
6.50 (1.64-25.76)
Baseline ISS
   I
33/50 (66.0)
20/48 (41.7)
2.72 (1.20-6.17)
   II
32/54 (59.3)
26/57 (45.6)
1.73 (0.82-3.68)
   III
23/40 (57.5)
12/40 (30.0)
3.16 (1.26-7.94)
Cytogenetic Risk
   High risk
10/20 (50.0)
9/18 (50.0)
1.00 (0.28-3.57)
   Standard risk
67/105 (63.8)
44/111 (39.6)
2.68 (1.55-4.66)
Baseline ECOG PS
   0
30/52 (57.7)
26/57 (45.6)
1.63 (0.76-3.47)
   ≥1
58/92 (63.0)
32/88 (36.4)
2.99 (1.63-5.48)
Abbreviations: CI, confidence interval; CR, complete response; D-VRd, DARZLEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance score; ISS, International Staging System; MRD, minimal residual disease; OR, odds ratio; TIE, transplant ineligible; VRd, bortezomib + lenalidomide + dexamethasone.

Prespecified Subgroup Analysis of PFS (TIE Subgroup)2
Subgroup
D-VRd
VRd
OR (95% CI)
Events/N
Median PFS, months
Events/N
Median PFS, months
Sex
   Male
23/65
NE
47/82
47.9
0.43 (0.26-0.70)
   Female
31/79
NE
29/63
59.9
0.76 (0.46-1.26)
Age
   <70 years
15/35
NE
20/35
59.9
0.60 (0.31-1.18)
   ≥70 years
39/109
NE
56/110
49.4
0.54 (0.36-0.82)
Region
   Europe
36/96
NE
48/90
49.6
0.55 (0.36-0.85)
   North America
11/31
NE
13/28
50.2
0.49 (0.22-1.10)
   Other
7/17
NE
15/27
68.0
0.78 (0.32-1.91)
Baseline ISS
   I
17/50
NE
25/48
60.5
0.52 (0.28-0.97)
   II
19/54
NE
30/57
49.4
0.50 (0.28-0.88)
   III
18/40
66.4
21/40
43.8
0.66 (0.35-1.24)
Cytogenetic Risk
   High risk
11/20
58.0
12/18
31.7
0.82 (0.36-1.87)
   Standard risk
35/105
NE
50/111
61.6
0.58 (0.38-0.89)
Baseline ECOG PS
   0
13/52
NE
28/57
59.9
0.33 (0.17-0.64)
   ≥1
41/92
74.8
48/88
47.2
0.70 (0.46-1.06)
Abbreviations: CI, confidence interval; D-VRd, DARZLEX FASPRO + bortezomib + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance score; ISS, International Staging System; NE, not estimable; OR, odds ratio; PFS, progression-free survival; TIE, transplant ineligible; VRd, bortezomib + lenalidomide + dexamethasone.
  • OS favored D-VRd vs VRd (HR, 0.84; 95% CI, 0.57-1.24) and when censoring for COVID-19-related deaths (HR, 0.74; 95% CI, 0.49-1.12).2
    • Deaths from COVID-19 occurred in 8 patients (5.6%) in the D-VRd arm and 3 patients (2.1%) in the VRd arm.
    • Deaths from progressive disease occurred in 8 patients (5.6%) in the D-VRd arm vs 17 patients (12.0%) in the VRd arm.
Safety

Safety Overview (TIE Subgroup)2
Event, n (%)
D-VRd
(n=144)
VRd
(n=142)
Any TEAE
144 (100.0)
142 (100.0)
   Grade 3/4
135 (93.8)
126 (88.7)
   Grade 5 non-COVID-19
18 (12.5)
13 (9.2)
   Grade 5 COVID-19a
6 (4.2)
1 (0.7)
Any serious TEAE
109 (75.7)
99 (69.7)
TEAE leading to discontinuation of study treatment
14 (9.7)
33 (23.2)
Exposure-adjusted grade 5 TEAE rate, patient-monthsb
0.30/100
0.26/100
Second primary malignancies
20 (13.9)
20 (14.1)
Most common (≥5%) grade 3/4 TEAEs of interest
   Neutropenia
65 (45.1)
47 (33.1)
   Thrombocytopenia
44 (30.6)
33 (23.2)
   Anemia
16 (11.1)
14 (9.9)
   Diarrhea
20 (13.9)
15 (10.6)
   Fatigue
13 (9.0)
15 (10.6)
   COVID-19c
14 (9.7)
5 (3.5)
   Pneumonia
26 (18.1)
19 (13.4)
   Peripheral sensory neuropathy
Any grade: 86 (59.7)
Grade 3/4: 14 (9.7)
Any grade: 91 (64.1)
Grade 3/4: 12 (8.5)
Abbreviations: D-VRd, DARZLEX FASPRO + bortezomib + lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; TIE, transplant ineligible; VRd, bortezomib + lenalidomide + dexamethasone.
aDeaths on or within 30 days of treatment.
bExposure-adjusted incidence rate: number of subjects with event per 100 patient-months at risk. Patient-months at risk = sum of exposure time until first TEAE occurrence or end of treatment for subjects without the event.
cGroup term.

Phase 2 Study of DARZALEX FASPRO in Combination with VMP in TIE NDMM

PLEIADES (MMY2040; NCT03412565) was a phase 2, non-randomized, open-label, multicenter study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with various treatment regimens in patients with MM, including D-VMP in TIE NDMM.3

Updated Efficacy and Safety Results of the PLEIADES Study

Moreau et al (2020)3 presented updated safety and efficacy results of the D-VMP arm in the PLEIADES study at a median follow-up of 25.2 months.

Results

Patient Characteristics

Key Baseline Demographics and Patient Characteristicsa,3
Characteristic
D-VMP
(n=67)
Age, years
   Median (range)
75 (66-86)
   18 to <65, n (%)
0 (0)
   65 to <75, n (%)
33 (49)
   ≥75, n (%)
34 (51)
Race, n (%)
   White
46 (69)
ECOG PS score, n (%)
   0
25 (37)
   1
38 (57)
   2
4 (6)
ISS disease stage, n (%)
   N
67
      I
22 (33)
      II
30 (45)
      III
15 (22)
Time since initial diagnosis, median (range), months
1.2 (0.5-5.3)
Bone marrow % plasma cells, n (%)
   N
67
      <10
3 (5)
      10-30
31 (46)
      >30
33 (49)
Cytogenetic profilec
   N
41
      Standard risk, n (%)
33 (81)
      High risk, n (%)
8 (20)
         t(4;14)
2 (5)
         t(14;16)
2 (5)
         del17p
4 (10)
Abbreviations: D-VMP, DARZALEX FASPRO + bortezomib + melphalan + prednisone; del, deletion; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System.
aAll-treated population, defined as patients who received ≥1 dose of study treatment.
bBased on the combination of serum β2-microglobulin and albumin.
cBased on fluorescence in situ hybridization/karyotype testing.
Efficacy
  • Response rates were similar to DARZALEX results in the ALCYONE study.3,6
    • In the D-VMP cohort (n=67):
      • ORR was 89.6% versus 90.9% in the ALCYONE study.
      • Stringent complete response (sCR) was 31.3% versus 23.1%.
      • CR was 23.9% versus 22.6%.
      • Very good partial response (VGPR) was 22.4% versus 27.1%.
      • Partial response (PR) was 11.9% versus 18%.
  • MRD-negativity rates were evaluated via next-generation sequencing (NGS) at a sensitivity threshold of 10-5.3 
    • MRD-negativity rate was 25.4%.
    • MRD-negative ≥CR rate was 25.4%.
Safety
  • A summary of TEAEs reported in the D-VMP cohort is presented in Table: Summary of TEAEs in D-VMP arm.3
  • Cardiac toxicities were infrequent (<5%).3 
  • Most patients with IRRs experienced them on the first administration (D-VMP, 83%).3 
  • IRRs were mild (grade 1/2); no patients reported grade 4 IRR.3 
  • Median time to onset of IRRs was 411 (range, 121-534) minutes.3 
  • Local injection site reactions occurred in 6% (11/198) of patients (all grade 1/2).3 

Summary of TEAEs in D-VMP Arma,3
D-VMP
(n=67)
Any-grade TEAE, n (%)
67 (100)
Grade 3/4 TEAE, n (%)
52 (78)
   Most common (≥5% in any cohort)
      Hypertension
6 (9)
      Thrombocytopenia
30 (45)
      Lymphopenia
15 (22)
      Anemia
13 (19)
      Neutropenia
25 (37)
      Insomnia
2 (3)
      Pneumonia
5 (7)
      Leukopenia
4 (6)
      Hyperglycemia
1 (1)
      Hypokalemia
2 (3)
      Diarrhea
2 (3)
      Lower respiratory tract infection
0
Grade 5 TEAEs, n (%)
3 (4)
Serious TEAEs, n (%)
30 (45)
TEAEs leading to treatment discontinuationb, n (%)
4 (6)
Any grade IRR, n (%)
6 (9)
Abbreviations: D-VMP, DARZALEX FASPRO + bortezomib + melphalan + prednisone; IRR, infusion-related reaction; TEAE, treatment-emergent adverse event.
aAll-treated population, defined as patients who received ≥1 dose of study treatment.
bD-VMP arm: neutropenic sepsis (n=1), hepatic neoplasm (n=1), cognitive disorder (n=1), and pneumonitis (n=1).

Phase 3 Study of DARZALEX FASPRO in Combination with Lenalidomide in TIE NDMM

IFM2017-03 (NCT03993912) was a phase 3, randomized, prospective, open-label, multicenter study assessing the safety and efficacy of D-R vs Rd in elderly frail patients with NDMM who were not eligible for high-dose chemotherapy and ASCT.4

Study Design/Methods

  • This study included patients aged ≥65 years who were diagnosed with NDMM and IFM frailty score ≥2 (age, ECOG PS, Charlson index).4
  • Eligible patients received DR or Rd until PD or unacceptable toxicity at the following dosage4,7:
    • D-R arm:
      • DARZALEX FASPRO: 1800 mg subcutaneously (SC) weekly (QW) for 8 weeks, every 2 weeks (Q2W) for 16 weeks, and every 4 weeks (Q4W) thereafter.
      • Lenalidomide: 25 mg orally (PO) on days 1 through 21 of each 28-day cycle, until progression.
      • Dexamethasone: 20 mg PO on days 1, 8, 15, and 22 of each 28-day cycle, until progression for the first 2 cycles, then discontinued.
    • Rd arm:
      • Lenalidomide: 25 mg PO on days 1 through 21 of each 28-day cycle, until progression.
      • Dexamethasone: 20 mg PO on days 1 through 21 of each 28-day cycle, until progression.
  • Primary endpoint: PFS.4
  • Key secondary endpoints: ORR, ≥VGPR rate, MRD-negativity rate, OS, and safety.4

Primary Analysis of the IFM2017-03 Study

 Manier et al (2025)4 reported results of the primary efficacy and safety analysis of the study at a median follow-up of 46.3 months.

Results

Patient Characteristics and Disposition

Demographic and Disease Characteristics at Baseline (ITT Population)4
Characteristic
D-R
(n=200)
Rd
(n=95)
Total
(N=295)
Median age (range), years
81 (68-92)
81 (68-90)
81 (68-92)
Age group, n (%)
   65 to <75 years
32 (16)
15 (16)
47 (16)
   75 to <80 years
49 (24)
19 (20)
 68 (23)
   ≥80 years
119 (60)
61 (64)
180 (61)
Sex, n (%)
   Female
102 (51)
49 (52)
151 (51)
   Male
98 (49)
46 (48)
144 (49)
ECOG performance status, n (%)
   0
21 (10)
9 (9)
30 (10)
   1
92 (46)
48 (51)
140 (47)
   2
76 (38)
35 (37)
111 (38)
   ≥3
11 (6)
3 (3)
14 (5)
Charlson Comorbidity index, n (%)
   ≤1
117 (58)
57 (60)
174 (59)
   >1
83 (42)
38 (40)
121 (41)
IFM frailty score, n (%)
   2
58 (29)
35 (37)
93 (32)
   3
80 (40)
27 (28)
107 (36)
   4
46 (23)
24 (25)
70 (24)
   5
16 (8)
9 (9)
25 (8)
ISS disease stage, n (%)
   I
33 (16)
19 (20)
52 (18)
   II
103 (52)
49 (52)
152 (52)
   III
64 (32)
27 (28)
91 (31)
Type of measurable disease, n (%)
   IgG
115 (57)
50 (53)
165 (56)
   IgA
36 (18)
20 (21)
56 (19)
   BJP
6 (3)
7 (7)
13 (4)
   SFLC
26 (13)
10 (11)
36 (12)
Cytogenetics profilea, n (%)
   Standard risk
146 (84)
56 (77)
202 (82)
   High risk
28 (16)
17 (23)
45 (18)
      del17p
16 (9)
11 (14)
27 (11)
      t(4;14)
9 (5)
5 (6)
14 (5)
      t(14;16)
5 (3)
2 (3)
7(3)
   NA
26
22
48
Creatinine clearance, n (%)
   <30 mL/min
0
3 (3)
3 (1)
   30 to <60 mL/min
121 (60)
50 (53)
171 (58)
   ≥60 mL/min
79 (40)
42 (44)
121 (41)
Abbreviations: BJP, Bence-Jones protein; D-R, DARZALEX FASPRO + lenalidomide; ECOG, Eastern Cooperative Oncology Group; IFM, Intergroupe Francophone Myeloma; Ig, immunoglobulin; ISS, International Staging System; ITT, intention-to-treat; NA, not applicable; Rd, lenalidomide + dexamethasone; SFLC, serum free light chanin.
adel17p, t(4;14), t(14;16).
  • At the data cutoff of November 6, 2024, a total of 119 patients (60%) in the D-R group and 84 patients (88%) in the Rd group had discontinued treatment, most commonly because of progressive disease (D-R vs Rd, respectively; 22% vs 41%) or AEs (18% vs 24%).4
  • Treatment exposures of patients in D-R and Rd groups are summarized in Table: Treatment Exposure.4
    • A total of 27 patients in the D-R group discontinued lenalidomide but continued to receive DARZALEX FASPRO as monotherapy.4
    • The median duration of DARZALEX FASPRO monotherapy was 17.2 months (range, 1.9-41.6).4

Treatment Exposure4
Parameter
D-R
(n=200)
Rd
(n=95)
Median treatment duration, months (IQR)
31.6 (12-45.3)
14.3 (5.2-30.3)
Median number of treatment cycles received (IQR)
33.5 (13.8-49.0)
16 (6.0-30.5)
Median relative dose intensity, % (IQR)
   DARZALEX FASPRO
95.2 (84.6-98.4)
-
   Lenalidomide
34.8 (22.3-57.1)
47.1 (29-75.8)
   Dexamethasone
-
53.1 (23.2-90.2)
Abbreviations: D-R, DARZALEX FASPRO + lenalidomide; IQR, interquartile range; Rd, lenalidomide + dexamethasone.
Efficacy
  • At a median follow-up of 46.3 months (95% CI, 44.9-47.6), disease progression or death occurred in 162 patients (D-R, 93 of 200 patients [46%]; Rd, 69 of 95 patients [73%]).7 Efficacy outcomes are detailed in Table: Efficacy Outcomes.4

Efficacy Outcomes4
Parameter
D-R
(n=200)
Rd
(n=95)
HR (95% CI)
P Value
Median PFSa, months (95% CI)
53.4 (35.3-NR)
22.5 (16.5-39)
0.51 (0.37-0.7)
<0.0001
Median OS, months
NR
47.2
 0.52 (0.35-0.77)
0.0001
4-year OS rate, %
68
47.8
-
-
ORR, %
91
86
-
0.005
   CR
34
12
-
-
   ≥VGPR
69
51
-
-
   VGPR
35
39
-
-
   PR
22
35
-
-
Abbreviations: CI, confidence interval; CR, complete response; D-R, DARZALEX FASPRO + lenalidomide; HR, hazard ratio; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; Rd, lenalidomide + dexamethasone; VGPR, very good partial response.
aA total of 93 and 63 events were reported in the DR and Rd arms, respectively.
  • Higher ≥VGPR rates observed as early as cycle 4 in the D-R vs /Rd group were 32% vs 20%, respectively (P=0.044).4
  • The MRD-negativity rate (10-5 sensitivity) in the D-R vs Rd group was 10% vs 4% and did not reach significance (P=0.11).4
  • The prespecified analysis of PFS confirmed the superiority of D-R over Rd across all subgroups. See Table: Prespecified Subgroup Analysis of PFS for details.4

Prespecified Subgroup Analysis of PFS4
Subgroup
D-R
(n=200)
Rd
(n=95)
HR (95% CI)
P Value
Events/
Patients
Median PFS (95% CI)
Events/
Patients
Median PFS (95% CI)
Age group
   ≤75 years
14/37 (38)
NR (42.1-NR)
12/18 (67)
24.6 (16.5-NR)
0.44 (0.20-0.95)
0.67
   76-80 years
23/44 (52)
37.7 (26.7-NR)
12/16 (75)
37.5 (20.2-NR)
0.71 (0.35-1.43)
   >80 years
51/108 (47)
48.6 (32.1-NR)
37/53 (70)
22.5 (14.3-42.9)
0.52 (0.34-0.79)
Sex
   Male
49/98 (50)
46.2 (33.2-NR)
37/46 (80)
18 (13.2-30.7)
0.44 (0.29-0.68)
0.48
   Female
44/102 (43)
54.2 (34.2-NR)
32/49 (65)
39 (20.1-47.8)
0.57 (0.36-0.89)
ECOG performance status
   0
9/21 (43)
53.6 (32.1-NR)
5/9 (56)
47.3 (19.4-NR)
0.75 (0.25-2.24)
0.17
   1
46/92 (50)
48.5 (30.9-NR)
34/48 (71)
36.2 (18.4-46.5)
0.63 (0.40-0.98)
   ≥2
38/87 (44)
53.4 (34.6-NR)
30/38 (79)
16.5 (10.3-28.5)
0.35 (0.22-0.58)
Charlson index
   ≤1
54/117 (46)
48.5 (31.6-NR)
43/57 (75)
22.8 (14.3-41.1)
0.49 (0.33-0.73)
0.82
   >1
39/83 (47)
53.6 (34.2-NR)
26/38 (68)
21.5 (16.2-47.8)
0.55 (0.34-0.91)
IFM frailty score
   2
23/58 (40)
NR (37.6-NR)
24/35 (69)
30.6 (20-47.3)
0.46 (0.26-0.82)
0.75
   3
39/80 (49)
46.2 (30.9-NR)
20/27 (74)
32.6 (16-53.1)
0.58 (0.34-0.99)
   4/5
31/62 (50)
35.3 (28.4-NR)
25/33 (76)
14.3 (8.4-36.2)
0.44 (0.25-0.75)
ISS stage
   I
12/33 (36)
NR (35.3-NR)
12/19 (63)
39 (16.5-NR)
0.46 (0.21-1.03)
0.97
   II
43/103 (42)
53.6 (46.2-NR)
35/49 (71)
26.2 (18.4-46.7)
0.48 (0.31-0.75)
   III
38/64 (59)
31.6 (26.7-NR)
22/27 (81)
14.3 (10.3-36.7)
0.53 (0.31-0.90)
Cytogenetic risk
   Standard
74/169 (44)
53.4 (37.4-NR)
55/78 (71)
30.6 (20-41.4)
0.52 (0.37-0.74)
0.66
   Higha
19/31 (61)
33.3 (20.3-NR)
14/17 (82)
13.7 (8.2-42.8)
0.42 (0.20-0.86)
Creatinine clearance
   ≤60 mL/min
56/121 (46)
53.4 (33.1-NR)
40/53 (75)
23.1 (19.4-42.8)
0.50 (0.33-0.76)
0.95
   >60 mL/min
37/79 (47)
48.6 (35.2-NR)
29/42 (69)
20.1 (13.2-41.4)
0.50 (0.31-0.82)
Abbreviations: CI, confidence interval; D-R, DARZALEX FASPRO + lenalidomide; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; IFM, Intergroupe Francophone du Myélome; ISS, International Staging System; NR, not reached; PFS, progression-free survival; Rd, lenalidomide + dexamethasone.
aA high-risk cytogenetic profile was defined by the detection of a del17p, t(14;16), or t(4;14) on fluorescence in situ hybridization or next-generation sequencing.
Safety

Most Common AEs and Secondary Primary Cancers Reported During Treatment in the Safety Population4
Parameter
D-R
(n=200)
Rd
(n=95)
Median treatment duration (months)
31.6
14.3
All AEs, n (%)
197 (98)
93 (98)
AEs of grade ≥3
178 (89)
75 (79)
   SAEs
126 (63)
66 (69)
   All grade 5
23 (12)
12 (13)
Hematologic, grade ≥3, n (%)
123 (62)
32 (34)
      Neutropenia
110 (55)
23 (24)
      Anemia
24 (12)
3 (3)
      Thrombocytopenia
19 (10)
5 (5)
Nonhematologic AEs, grade ≥3, n (%)
132 (66)
68 (72)
      Infection
38 (19)
20 (21)
         Pneumonia
11 (6)
8 (8)
         COVID-19
11 (6)
4 (4)
   Fatigue
8 (4)
8 (8)
   Gastrointestinal disorder
14 (7)
5 (5)
   Second primary malignancies
14 (7)
10 (11)
      Noncutaneous
12 (6)
6 (6)
      Cutaneous
2 (1)
4 (4)
Infection rate per patient per year, %
0.07
0.09
Treatment discontinuation due to AEs, n (%)
36 (18)
23 (24)
Abbreviations: AE, adverse event; COVID-19, coronavirus disease 2019; D-R, DARZALEX FASPRO + lenalidomide; Rd, lenalidomide + dexamethasone; SAE, serious adverse event.
  • Deaths were reported in 104 patients: 59 (30%) in the D-R group and 45 (47%) in the Rd group.4

LITERATURE SEARCH

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 02 June 2026.

 

References

Show
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5 Facon T, Zweegman S, Hungria V, et al. Daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) in patients with newly diagnosed multiple myeloma (NDMM): Subgroup analysis of transplant-ineligible (TIE) patients in the phase 3 CEPHEUS study. Oral Presentation presented at: The American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2025; Chicago, USA.  
6 Mateos MV, 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(10218):132-141.  
7 Manier S, Lambert J, Hulin C, et al. A dexamethasone sparing-regimen with daratumumab and lenalidomide in frail patients with newly diagnosed multiple myeloma: the phase 3 IFM2017-03 trial. Oral Presentation presented at: The 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2024; San Diego, CA.