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DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)
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DARZALEX + DARZALEX FASPRO - Use in Combination with Lenalidomide and Dexamethasone in Multiple Myeloma

Last Updated: 09/14/2026

SUMMARY

  • MAIA is a phase 3 study evaluating the safety and efficacy of DARZALEX for intravenous (IV) use in combination with lenalidomide and dexamethasone (D-Rd) compared to lenalidomide plus dexamethasone (Rd) in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients.1-3
    • Facon et al (2026)4 published the final survival analysis of the MAIA study at a median follow-up of 89.3 months. The median overall survival (OS) was 90.3 months in the D-Rd arm vs 64.1 months in the Rd arm (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.55-0.82). Death was reported in 48% of patients in the D-Rd group vs 60% of patients in the Rd group, primarily due to disease progression.
    • Other relevant subgroup analyses from MAIA Study have been referenced below.5-12
  • POLLUX was a phase 3 study evaluating the safety and efficacy of Rd and D-Rd in patients with relapsed or refractory multiple myeloma (RRMM).13
    • Dimopoulos et al (2023)14 reported updated efficacy and safety results from POLLUX at a median follow-up of 79.7 months. Median OS in the intention-to-treat (ITT) population with D-Rd was 67.6 months (95% CI, 53.1-80.5) with D-Rd and
      51.8 months (95% CI, 44.0-60.0) with Rd (HR, 0.73; 95% CI, 0.58-0.91; P=0.0044). The most common grade 3/4 (≥10%) TEAEs were neutropenia (D-Rd, 57.6%; Rd, 41.6%), anemia (D-Rd, 19.8%; Rd, 22.4%), pneumonia (D-Rd, 17.3%; Rd, 11%), thrombocytopenia (D-Rd, 15.5%; Rd, 15.7%), and diarrhea (D-Rd, 10.2%; Rd, 3.9%).
    • Other relevant subgroup analyses from POLLUX Study have been referenced below.15-20
  • PLEIADES is a phase 2 study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with 4 standard-of-care treatment regimens in patients with multiple myeloma (MM).21-24
    • Moreau et al (2020)25 presented the updated safety and efficacy results of the D-Rd, DARZALEX FASPRO in combination with carfilzomib and dexamethasone (D-Kd), and DARZALEX FASPRO in combination with bortezomib, melphalan, and prednisone (D-VMP) arms of the PLEIADES study. Results specific to the D-Rd cohort are summarized below.
  • Other relevant literature that has been identified has been referenced below.26,27

PRODUCT LABELING

Clinical studies

Phase 3 Study of DARZALEX in Combination with 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 autologous stem cell transplantation (ASCT).1-3

Study Design/Methods

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

Final Survival Analysis of the MAIA Study

Facon et al (2026)4 published the final survival analysis of the MAIA study at a median follow-up of 89.3 months (range, 0-102.2) in the ITT population.

Results

Patient Characteristics
  • A total of 737 (D-Rd, n=368; Rd, n=369) patients were randomized in this study.4
  • The median follow-up was 89.6 months (range, 0.0-99.9) in the D-Rd group and 88.9 months (range, 0.0-102.2) in the Rd group.4
  • By the clinical cutoff of November 30, 2023, 285/364 patients (78%) in the D-Rd arm and 345/365 patients (95%) in the Rd arm discontinued treatment.4 
  • Baseline characteristics of the intention-to-treat (ITT) population are summarized in Table: Demographic and Baseline Disease Characteristics (ITT Population; MAIA).28

Demographic and Baseline Disease Characteristics (ITT Population; MAIA)28
Characteristic
D-Rd
(n=368)
Rd
(n=369)
Age
   Median (range), years
73.0 (50-90)
74.0 (45-89)
ECOG PSa, n (%)
   0
127 (34.5)
123 (33.3)
   1
178 (48.4)
187 (50.7)
   ≥2
63 (17.1)
59 (16.0)
ISS disease stageb, n (%)
   I
98 (26.6)
103 (27.9)
   II
163 (44.3)
156 (42.3)
   III
107 (29.1)
110 (29.8)
Type of measurable disease, n (%)
   IgG
225 (61.1)
231 (62.6)
   IgA
65 (17.7)
66 (17.9)
   Otherc
9 (2.4)
10 (2.7)
   Detected in urine only
40 (10.9)
34 (9.2)
   Detected in serum FLC only
29 (7.9)
28 (7.6)
Cytogenetic riskd
   N
319
323
   Standard risk, n (%)
271 (85.0)
279 (86.4)
   High risk, n (%)
48 (15.0)
44 (13.6)
Abbreviations: del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FLC, free light chain; Ig, immunoglobulin; ISS, International Staging System; ITT, intention-to-treat; MM, multiple myeloma; Rd, lenalidomide + dexamethasone; t, translocation.
aECOG PS is scored on a scale of 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bISS disease stage was based on the combination of serum β2-microglobulin and albumin.
cIncludes IgD, IgE, IgM, and biclonal disease.
dCytogenetic risk was assessed by fluorescence in situ hybridization or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del(17p).
Efficacy
  • At the median follow-up of 89.3 months, 175 patients (48%) in the D-Rd arm and 218 patients (59%) in the Rd arm had died.4
  • The median OS was 90.3 months in the D-Rd arm vs 64.1 months in the Rd arm (HR, 0.67; 95% CI, 0.55-0.82).4
  • The estimated 7-year OS rate was 53.1% (95% CI, 47.8-58.2) for the D-Rd arm and 39.3% (95% CI, 34.1-44.5) for the Rd arm.4
  • Prespecified subgroup analyses of OS are summarized in Table: Analysis of OS in Pre-Specified Patient Subgroups (ITT Population).4

Analysis of OS in Pre-Specified Patient Subgroups (ITT Population)4
Subgroup
D-Rd
Rd
HR (95% CI)
n/N
Median OS, Months
n/N
Median OS, Months
Sex
   Male
95/189
82.5
120/195
60.6
0.72 (0.55-0.94)
   Female
80/179
NE
98/174
67.8
0.66 (0.49-0.89)
Age
   <75 years
84/208
NE
107/208
79.6
0.69 (0.52-0.92)
   ≥75 years
91/160
72.3
111/161
54.8
0.67 (0.51-0.88)
Race
   White
161/336
92.7
197/339
65.5
0.71 (0.57-0.87)
   Other
14/32
90.3
21/30
49.1
0.50 (0.25-0.99)
Region
   North America
46/101
92.7
64/102
54.8
0.57 (0.39-0.83)
   Other
129/267
90.3
154/267
66.8
0.74 (0.58-0.93)
Baseline renal function (CrCl)
   >60 mL/min
99/206
92.7
123/227
69.9
0.78 (0.60-1.01)
   ≤60 mL/min
76/162
90.3
95/142
54.4
0.57 (0.42-0.77)
Baseline hepatic function
   Normal
156/335
NE
203/340
63.8
0.65 (0.53-0.80)
   Impaireda
19/31
63.5
15/29
87.4
1.31 (0.66-2.58)
ISS disease stage
   I
34/98
NE
42/103
NE
0.79 (0.50-1.24)
   II
77/163
92.7
95/156
61.7
0.63 (0.46-0.85)
   III
64/107
65.2
81/110
47.3
0.68 (0.49-0.95)
Type of MM
   IgG
111/225
87.2
132/231
69.3
0.78 (0.60-1.00)
   Non-IgG
35/74
86.4
49/76
53.7
0.58 (0.37-0.89)
Cytogenetic risk at study entryb
   High risk
31/48
55.6
36/44
42.5
0.65 (0.40-1.06)
   Standard risk
122/271
NE
160/279
65.5
0.66 (0.52-0.84)
ECOG PS
   0
48/127
NE
56/123
NE
0.76 (0.52-1.12)
   1
86/178
92.7
118/187
58.3
0.64 (0.48-0.84)
   ≥2
41/63
62.8
44/59
39.0
0.68 (0.44-1.04)
Abbreviations: AST, aspartate aminotransferase; CI, confidence interval; CrCl, creatinine clearance; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IgG, immunoglobulin G; ISS, International Staging System; ITT, intention-to-treat; MM, multiple myeloma; NE, not estimable; OS, overall survival; Rd, lenalidomide + dexamethasone; ULN, upper limit of normal.
aImpaired hepatic function included mild (total bilirubin ≤ULN and AST>ULN, or total bilirubin >ULN but ≤1.5×ULN), moderate (total bilirubin >1.5×ULN but ≤3×ULN), and severe (total bilirubin >3×ULN) impairment.
bPatients with high cytogenetic risk were positive by fluorescence in situ hybridization or karyotype testing for ≥1 of the following cytogenetic abnormalities: del(17p), t(14;16), or t(4;14).

Analysis of OS Across Age Subgroups (ITT Population)4
Age Subgroup
D-Rd
Rd
HR (95% CI)
Median OS, Months
Median OS, Months
<70 years
NR
NR
0.66 (0.40-1.08)
≥70 to <75 years
NR
77.6
0.70 (0.50-1.00)
≥75 years
72.3
54.8
0.67 (0.51-0.88)
≥80 years
67.6
48.9
0.64 (0.42-0.97)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HR, hazard ratio; ITT, intention-to-treat; MM, multiple myeloma; NR, not reached; OS, overall survival; Rd, lenalidomide + dexamethasone.
  • Patients who achieved MRD negativity and sustained MRD negativity (10-5) had prolonged OS vs patients who did not and patients who received D-Rd demonstrated prolonged OS vs patients who received Rd, regardless of MRD status.4
  • Median time to subsequent antimyeloma therapy was NR (95% CI, 84.1-NE) in the D-Rd arm vs 42.4 months (95% CI, 33.5-50.6) in the Rd arm (HR, 0.51; 95% CI, 0.41-0.63; P<0.0001).4
Safety

Summary of Death and Causes of Death (Safety Population)4
n (%)
D-Rd
(n=364)
Rd
(n=365)
Total number of patients who died during the study
173 (48)
218 (60)
   Primary cause of death
      Disease progression
76 (21)
88 (24)
      Adverse events
44 (12)
40 (11)a
         Related to study treatmentb
14 (4)
10 (3)
         Unrelated to study treatment
28 (8)
29 (8)
         COVID-19
2 (1)
0
      Otherc
53 (15)
90 (25)
         Infections/infestations
9 (2)
30 (8)
         General disorders/administration site conditionsd
11 (3)
5 (1)
         Neoplasms (benign, malignant, or unspecified)
11 (3)
4 (1)
         Cardiac disorders
1 (<1)
8 (2)
         Nervous system disorders
3 (1)
5 (1)
         Unknown
13 (4)
27 (7)
Deaths within 30 days of last study treatment dose
31 (9)
35 (10)
   Primary cause of death
      Disease progression
1 (<1)
1 (<1)
      Adverse events
29 (8)
32 (9)
         Related to study treatmentb
11 (3)
10 (3)
         Unrelated to study treatment
18 (5)
22 (6)
      Othere
1 (<1)
2 (1)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide/dexamethasone.
aOne patient in the Rd group had an adverse event as the primary cause of death, but it was not specified by the investigator whether the event was considered related or unrelated to study treatment.
bAdverse events were related to ≥1 of the three components of study treatment: daratumumab, lenalidomide, and dexamethasone.
cOther reasons were reported in ≥1% of patients in either treatment group.
dAll events were related to the general health condition of the patient.
eIncludes a nervous system disorder in one patient in the D-Rd group and a blood and lymphatic system disorder and general disorder/administration site condition in one patient each in the Rd group.

Phase 3 Study of DARZALEX in Combination with Rd in Patients with RRMM

POLLUX (MMY3003; NCT02076009) is a phase 3, randomized, open-label, multicenter study to evaluate the safety and efficacy of D-Rd and Rd in patients with RRMM.13

Updated Efficacy and Safety Results of the POLLUX Study

Dimopoulos et al (2023)14 reported updated results of the POLLUX study, including OS, at a median follow-up of 79.7 months.

Results

Patients and Treatments

Baseline Demographics and Clinical Characteristics (POLLUX; ITT Population)14
Characteristic
D-Rd
(n=286)
Rd
(n=283)
Age, years
   Median (range)
65 (34-89)
65 (42-87)
   ≥75, n (%)
29 (10.1)
35 (12.4)
ISS staginga, n (%)
   I
137 (47.9)
140 (49.5)
   II
93 (32.5)
86 (30.4)
   III
56 (19.6)
57 (20.1)
Median (range) time from diagnosis, years
3.48 (0.4-27.0)
3.95 (0.4-21.7)
Prior lines of therapy, n (%)
   Median (range)
1 (1-11)
1 (1-8)
   1
149 (52.1)
146 (51.6)
   2
85 (29.7)
80 (28.3)
   3
38 (13.3)
38 (13.4)
   >3
14 (4.9)
19 (6.7)
Prior IMiD, n (%)
158 (55.2)
156 (55.1)
   Prior thalidomide
122 (42.7)
125 (44.2)
   Prior lenalidomide
50 (17.5)
50 (17.7)
Prior PI, n (%)
245 (85.7)
242 (85.5)
   Prior bortezomib
241 (84.3)
238 (84.1)
Prior PI+ IMiD, n (%)
125 (43.7)
125 (44.2)
Refractory to bortezomib, n (%)
59 (20.6)
58 (20.5)
Refractory to last line of prior therapy, n (%)
80 (28)
76 (26.9)
Cytogenetic risk profileb, n/N (%)
   Standard risk
193/228 (84.6)
176/211 (83.4)
   High risk
35/228 (15.4)
35/211 (16.6)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; IMiD, immunomodulatory drug; ISS, International Staging System; ITT, intention-to-treat; PI, proteasome inhibitor; Rd, lenalidomide + dexamethasone.
aISS staging was based on the combination of serum β2-microglobulin and albumin.
bCytogenetic risk was assessed locally by fluorescence in situ hybridization or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del17p abnormality.
Efficacy
  • At a median follow-up of 79.7 months, D-Rd arm provided a 27% reduction in the risk of death compared to Rd arm (HR, 0.73; 95% CI, 0.58-0.91; P=0.0044).
    • Median OS in the ITT population with D-Rd was 67.6 months (95% CI, 53.1-80.5) vs 51.8 months (95% CI, 44.0-60.0) with Rd.
  • MRD-negativity rate at a 10-5 sensitivity threshold was 33.2% vs 6.7% in the D-Rd vs Rd arms, respectively (P<0.0001).
  • In the ITT population, median disease progression on the next line of therapy or death (PFS2) was significantly prolonged in D-Rd vs Rd arms, respectively, at 57.9 months vs 32.0 months (HR, 0.54; 95% CI, 0.43-0.67; P<0.0001).
  • In total, 44.9% (127 of 283) of patients vs 74.7% (210 of 281) of patients in the D-Rd vs Rd arms, respectively, received subsequent therapy. See Table: Most Common Subsequent Anticancer Therapies in the D-Rd and Rd arms.
    • Of the patients in the Rd arm who received subsequent therapy, 122 (58.1%) patients received DARZALEX in any subsequent line of therapy.
    • Median number of subsequent lines of therapy was 2 (range, 1-13) vs 2 (range, 1-12) in the D-Rd vs Rd arms, respectively.
  • Median time to subsequent treatment was significantly increased with D-Rd vs Rd (69.3 vs 23.1 months; HR, 0.40; 95% CI, 0.32-0.50; P<0.0001).
  • The most common first line subsequent anticancer therapy was pomalidomide and dexamethasone (12.5%) or bortezomib and dexamethasone (10.2%) in the D-Rd arm and DARZALEX monotherapy (22.4%) in the Rd arm.

Most Common Subsequent Anticancer Therapies in the D-Rd and Rd arms14
Drug, %
D-Rd
Rd
Dexamethasone
39.2
63.0
Daratumumab
-
43.4
Pomalidomide
23.7
37.0
Bortezomib
19.8
33.8
Cyclophosphamide
17.7
38.1
Carfilzomib
16.6
23.5
Lenalidomide
-
18.5
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone.
Safety

Most Common (>15% of Patients) and Grade 3/4 (>5% of Patients) TEAEs in the Safety Population14
TEAE, n (%)
All Grades
Grade 3/4
D-Rd
(n=283)
Rd
(n=281)
D-Rd
(n=283)
Rd
(n=281)
Hematologic
   Neutropenia
185 (65.4)
136 (48.4)
163 (57.6)
117 (41.6)
   Anemia
121 (42.8)
117 (41.6)
56 (19.8)
63 (22.4)
   Thrombocytopenia
93 (32.9)
90 (32.0)
44 (15.5)
44 (15.7)
   Lymphopenia
20 (7.1)
17 (6.0)
17 (6.0)
12 (4.3)
   Febrile neutropenia
18 (6.4)
8 (2.8)
18 (6.4)
8 (2.8)
Nonhematologic
   Diarrhea
170 (60.1)
108 (38.4)
29 (10.2)
11 (3.9)
   URIT
125 (44.2)
79 (28.1)
6 (2.1)
5 (1.8)
   Fatigue
119 (42.0)
87 (31.0)
20 (7.1)
12 (4.3)
   Cough
107 (37.8)
43 (15.3)
1 (0.4)
0 (0.0)
   Nasopharyngitis
100 (35.3)
62 (22.1)
0 (0.0)
0 (0.0)
   Constipation
95 (33.6)
77 (27.4)
4 (1.4)
2 (0.7)
   Muscle spasms
87 (30.7)
61 (21.7)
3 (1.1)
5 (1.8)
   Nausea
87 (30.7)
53 (18.9)
6 (2.1)
2 (0.7)
   Insomnia
80 (28.3)
65 (23.1)
6 (2.1)
6 (2.1)
   Pneumonia
80 (28.3)
49 (17.4)
49 (17.3)
31 (11)
   Back pain
77 (27.2)
59 (21.0)
10 (3.5)
5 (1.8)
   Pyrexia
77 (27.2)
41 (14.6)
9 (3.2)
7 (2.5)
   Arthralgia
75 (26.5)
56 (19.9)
4 (1.4)
4 (1.4)
   Peripheral edema
72 (25.4)
50 (17.8)
3 (1.1)
4 (1.4)
   Dyspnea
67 (23.7)
39 (13.9)
15 (5.3)
2 (0.7)
   Vomiting
66 (23.3)
20 (7.1)
3 (1.1)
4 (1.4)
   Bronchitis
63 (22.3)
50 (17.8)
9 (3.2)
9 (3.2)
   Cataract
61 (21.6)
35 (12.5)
21 (7.4)
13 (4.6)
   Asthenia
59 (20.8)
47 (16.7)
10 (3.5)
9 (3.2)
   Hypokalemia
58 (20.5)
35 (12.5)
19 (6.7)
12 (4.3)
   Headache
57 (20.1)
23 (8.2)
0 (0.0)
0 (0.0)
   Rash
51 (18.0)
36 (12.8)
1 (0.4)
0 (0.0)
   Decreased appetite
50 (17.7)
37 (13.2)
6 (2.1)
1 (0.4)
   Pain in extremity
48 (17.0)
42 (14.9)
0 (0.0)
1 (0.4)
   Influenza
46 (16.3)
24 (8.5)
11 (3.9)
3 (1.1)
   Hypophosphatemia
22 (7.8)
14 (5.0)
16 (5.7)
8 (2.8)
   Syncope
16 (5.7)
4 (1.4)
15 (5.3)
4 (1.4)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; URTI, Upper respiratory tract infection.

TEAEs Leading to Treatment Discontinuation or Deaths14
TEAEs
D-Rd
(n=283)
Rd
(n=281)
Serious TEAEs, %
72.4
52.7
   Pneumonia
17.0
11.4
TEAEs leading to treatment discontinuation, %
19.1
16.0
   Infections, n (%)
13 (4.6)
11 (3.9)
TEAEs leading to death, n (%)
35 (12.4)
24 (8.5)
   Septic shock, %
1.4
0.4
   Cardiac arrest, %
1.1
0.4
   Sudden death, %
1.1
0.4
   Pneumonia, %
0.7
1.1
   Acute kidney injury, %
0.4
1.1
   Sepsis, %
0
1.1
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event.

Phase 2 Study of DARZALEX FASPRO in Combination with 4 Standard-of-Care Regimens in MM

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.

Updated Analysis of the D-Rd, D-VMP, and D-Kd Cohorts of the PLEAIDES Study

Moreau et al (2020)25 presented updated safety and efficacy results for D-Rd, D-Kd, and D-VMP arms of the PLEIADES study. Results specific to the D-Rd arm at a median follow up of 25.7 months are summarized below.

Results: D-Rd Cohort at a Median Follow-up of 25.7 Months

Patient Characteristics and Disposition

Baseline Demographics and Patient Characteristics - D-Rd Cohorta,24
RRMM With ≥ 1 Prior Line of Therapy
D-Rd (n=65)
Age, years
   Median (range)
69 (33-82)
   18 to <65, n (%)
22 (33.8)
   65 to <75, n (%)
29 (44.6)
   ≥75, n (%)
14 (21.5)
Male, n (%)
45 (69.2)
Median (range) body weight, kg
80.6 (54-143)
Race, n (%)
   White
45 (69.2)
   Black or African American
2 (3.1)
   Asian
0 (0.0)
ECOG PS score, n (%)
   0
36 (55.4)
   1
29 (44.6)
   2
0 (0.0)
Median (range) number of prior lines of therapy, n
1 (1-5)
ISS stagingb, n (%)
   I
27 (41.5)
   II
19 (29.2)
   III
18 (27.7)
Cytogenic riskc, d, n (%)
n=31
   Standard risk
20 (64.5)
   High risk
11 (35.5)
   t(4;14)
6 (19.4)
   t(14;16)
3 (9.7)
   del17p
4 (12.9)
Abbreviations: D-Rd, DARZALEX FASPRO + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, international staging system; RRMM, relapsed or refractory multiple myeloma.
aAll-treated population, defined as patients who received ≥1 dose of study treatment.
bBased on the combination of serum β2-microglobulin and albumin at screening.
cBased on fluorescence in situ hybridization or karyotyping testing conducted locally.
dHigh cytogenetic risk was defined as having ≥1 of t(4;14), t(14;16) or del17p abnormalities.
Efficacy
  • Response rates were similar to DARZALEX studies in POLLUX.29
    • In the D-Rd cohort (n=65):
      • ORR was 93.8% vs 92.9% in the POLLUX study.29
      • sCR was 23.1% vs 29.5%.
      • CR was 26.2% vs 28.1%.
      • VGPR was 30.8% vs 23.5%.
      • PR was 13.8% vs 11.7%.
  • MRD-negativity rates were evaluated via NGS at a sensitivity threshold of 10-5.25
    • MRD-negativity rate was 20.0% in the D-Rd cohort.
    • MRD-negative ≥CR rate was 20.0% in the D-Rd cohort.
Safety
  • A summary of TEAEs reported is presented in Table: Summary of TEAEs in D-Rd Cohort.25
  • Cardiac toxicities were infrequent (<5%) in D-Rd cohort.25
  • Most patients with IRRs experienced them on the first administration (D-Rd, 100%).
  • IRRs were mild (grade 1/2).25
  • Median (range) time to onset of IRRs was 330 (254-330) minutes in the D-Rd cohort.25
  • Local injection site reactions occurred in 6% (11/198) of patients (all grade 1/2).25

Summary of TEAEs in D-Rd Cohorta,25
n (%)
RRMM With ≥1 Prior Line of Therapy
D-Rd (n=65)
Any-grade TEAE
65 (100)
Grade 3/4 TEAE
61 (94)
   Most common hematologic TEAEs (≥5% in any cohort)
      Thrombocytopenia
9 (14)
      Lymphopenia
7 (11)
      Anemia
6 (9)
      Neutropenia
36 (55)
      Leukopenia
6 (9)
   Most common nonhematologic TEAEs (≥5% in any cohort)
      Hypertension
8 (12)
      Insomnia
3 (5)
      Pneumonia
10 (15)
      Hyperglycemia
6 (9)
      Hypokalemia
4 (6)
      Diarrhea
4 (6)
      Lower respiratory tract infection
4 (6)
Grade 5 TEAE
2 (3)
Serious TEAEs
36 (55)
TEAEs leading to treatment discontinuationb
6 (9)
Any-grade IRR
3 (5)
Abbreviations: D-Rd, DARZALEX FASPRO + lenalidomide + dexamethasone; IRR, infusion-related reaction; RRMM, relapsed or refractory multiple myeloma; TEAE, treatment-emergent adverse event.
aAll-treated population, defined as patients who received ≥1 dose of study treatment.
bPneumonia (n=2), diverticulitis (n=1), enterobacter infection (n=1), myocardial infarction (n=1), and face edema (n=1).

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 02 September 2026. For purposes of streamlining, this scientific response has been limited to phase 2/3 clinical studies.

In response to your specific request, summarized in this response is the relevant data from company-sponsored studies pertaining to this topic.

 

References

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2 Facon T, Kumar SK, Plesner T, et al. Phase 3 randomized study of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (NDMM) ineligible for transplant (MAIA). Oral presentation presented at: 60th American Society of Hematology (ASH) Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA.  
3 Facon T, Moreau P, Weisel K, et al. Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. Leukemia. 2025;39(4):942-950.  
4 Facon T, Kumar SK, Orlowski RZ, et al. Daratumumab, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: MAIA final survival analysis. Leukemia. 2026;:1-10.  
5 Facon T, Kumar S, Weisel K, et al. Daratumumab plus lenalidomide and dexamethasone in patients with transplant-ineligible newly diagnosed multiple myeloma: MAIA age subgroup analysis. 2022;(Poster).  
6 Moreau P, Facon T, Usmani S, et al. Daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): clinical assessment of key subgroups of the phase 3 MAIA study. 2022;(Poster).  
7 Facon T, Kumar S, Plesner T, et al. Time to response, duration of response, and patient-reported outcomes (PROs) with daratumumab (DARA) plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): subgroup analysis of the phase 3 MAIA study. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL/Virtual Meeting.  
8 Facon T, Cook G, Usmani SZ, et al. Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA. Leukemia. 2022;36(4):1066-1077.  
9 San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity with daratumumab in newly diagnosed multiple myeloma: MAIA and ALCYONE. Blood. 2022;139:492-501.  
10 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-.  
11 Facon T, Plesner T, Usmani S, et al. Health-related quality of life for frail transplant-ineligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide and dexamethasone: subgroup analysis of MAIA trial. Poster presented at: 4th European Myeloma Network (EMN) Meeting; April 20-22, 2023; Amsterdam.  
12 Moreau P, Facon T, Usmani SZ, et al. Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study. Leukemia. 2025;39(3):710-719.  
13 Dimopoulos M, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(14):1319-1331.  
14 Dimopoulos MA, Oriol A, Nahi H, et al. Overall survival with daratumumab, lenalidomide, and dexamethasone in previously treated multiple myeloma (POLLUX): a randomized, open-label, phase III trial. J Clin Oncol. 2023;41(8):1590-1599.  
15 Spencer A, Moreau P, Mateos M, et al. Daratumumab in combination with bortezomib plus dexamethasone (D-Vd) or lenalidomide plus dexamethasone (D-Rd) in relapsed or refractory multiple myeloma (RRMM): subgroup analysis of the phase 3 CASTOR and POLLUX studies in patients with early or late relapse after initial therapy. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL/Virtual Meeting.  
16 Mateos M, Richardson P, Weisel K, et al. Daratumumab (DARA) plus bortezomib and dexamethasone (D-Vd) or lenalidomide and dexamethasone (D-Rd) in relapsed or refractory multiple myeloma (RRMM): subgroup analyses of CASTOR and POLLUX. 2022;(Poster).  
17 Plesner T, Dimopoulos M, Oriol A, et al. Health-related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial. Br J Haematol. 2021;194:132-139.  
18 Kaufman J, Dimopoulos M, White D, et al. Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX. Blood Cancer J. 2020;10(11):111.  
19 Usmani S, Mateos M, Lentzsch S, et al. Efficacy of daratumumab in combination with standard-of-care regimens in lenalidomide-exposed or -refractory patients with relapsed/refractory multiple myeloma (RRMM): analysis of the CASTOR, POLLUX, and MMY1001 studies. Poster presented at: 60th American Society of Hematology (ASH) Annual Meeting & Exposition Poster; December 1-4, 2018; San Diego, CA.  
20 Spencer A, Moreau P, Mateos MV, et al. Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX. Blood Advances. 2024;8(2):388-398.  
21 H SMJCA Goldschmidt. Subcutaneous (SC) daratumumab (DARA) in combination with standard multiple myeloma (MM) treatment regimens: an open-label, multicenter phase 2 study (PLEIADES). 2019.  
22 Chari A, Goldschmidt H, Yang S, et al. Subcutaneous daratumumab plus carfilzomib and dexamethasone in relapsed/refractory multiple myeloma: an open-label, multicenter, phase 2 study (PLEIADES). Poster presented at: 17th International Myeloma Workshop (IMW); September 12-15, 2019; Boston, MA.  
23 Chari A, Miguel J, McCarthy H, et al. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy: PLEIADES study update. Poster presented at: 61st American Society of Hematology (ASH) Annual Meeting; December 7-10, 2019; Orlando, FL.  
24 Chari A, Rodriguez-Otero P, McCarthy H, et al. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label phase II study. Br J Haematol. 2021;192(5):869-878.  
25 Moreau P, Chari A, Haenel M, et al. Subcutaneous daratumumab (DARA SC) plus standard-of-care (SoC) regimens in multiple myeloma (MM) across lines of therapy in the phase 2 PLEIADES study: initial results of the DARA SC plus carfilzomib/dexamethasone (D-Kd) cohort, and updated results for the DARA SC plus bortezomib/melphalan/prednisone (D-VMP) and DARA SC plus lenalidomide/dexamethasone (D-Rd) cohorts. Poster presented at: 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual.  
26 Wang J, Arroyo-Suarez R, Dasari S, et al. Early versus late response to daratumumab-based triplet therapies in patients with multiple myeloma: a pooled analysis of trials POLLUX, CASTOR and MAIA. Leuk Lymphoma. 2022;63(7):1669-1677.  
27 Perrot A, Facon T, Plesner T, et al. Sustained improvement in health‐related quality of life in transplant‐ineligible newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, and dexamethasone: MAIA final analysis of patient‐reported outcomes. Eur J Haematol. 2025;114(5):883-889.  
28 Facon T, Kumar SK, Orlowski R, et al. Final survival analysis of daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma: MAIA study. Poster presented at: The European Hematology Association (EHA) Hybrid Congress; June 13-16, 2024; Madrid, Spain.  
29 Kaufman JL, Usmani S, Miguel J, et al. Four-year follow-up of the phase 3 POLLUX study of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in relapsed or refractory multiple myeloma (RRMM). Poster presented at: 61st American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL.  

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