J&J Medical Connect
DARZALEX FASPRO®

(daratumumab and hyaluronidase-fihj)

J&J Medical Connect

Connect with us

Connect with us

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)

Medical Information

DARZALEX + DARZALEX FASPRO - Use in Patients with Renal Impairment and Multiple Myeloma

Last Updated: 04/01/2026

Summary

  • No formal studies of DARZALEX for intravenous (IV) use or DARZALEX FASPRO for subcutaneous (SC) use in patients with renal impairment have been conducted. Based on population pharmacokinetic (PK) analyses, no dosage adjustment is necessary in patients with renal impairment.1,2
  • As an IgG1κ monoclonal antibody, renal excretion and hepatic enzyme-mediated metabolism of intact daratumumab are unlikely to represent major elimination routes.2
  • Patients with severe renal impairment were excluded from DARZALEX and DARZALEX FASPRO clinical studies and no formal clinical or PK studies have been conducted in patients receiving hemodialysis or peritoneal dialysis.
  • Moreau et al (2025)3 reported the efficacy and safety results in clinically important subgroups of patients with newly diagnosed multiple myeloma (NDMM) from the MAIA study. The progression-free survival (PFS) duration was longer in the DARZALEX in combination with lenalidomide and dexamethasone (D-Rd) vs lenalidomide in combination with dexamethasone (Rd) arm in most subgroups. Treatment with D-Rd generally resulted in a greater improvement in the overall response rate (ORR), minimal residual disease (MRD)-negativity (10-5) rate, and sustained MRD-negativity (10-5) rate for ≥12 months across subgroups, compared with Rd. Among patients aged ≥75 years, grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 95.5% vs 95.0% patients in the D-Rd vs Rd arm.
  • Facon et al (2022)4 presented the results of a subgroup analysis of the MAIA study that evaluated the efficacy and patient-reported outcomes (PROs) of D-Rd vs Rd in patients with NDMM who had renal impairment and/or high-risk cytogenetics. In the renal function subgroups, median times to very good partial response or better (≥VGPR) and complete response or better (≥CR) were shorter and durations of ≥CR and partial response or better (≥PR) were longer in the D-Rd vs Rd arm.
  • Mateos et al (2022)5 presented the results of a post hoc subgroup analysis of the CASTOR and POLLUX studies, evaluating the efficacy of DARZALEX in combination with bortezomib plus dexamethasone (D-Vd) vs bortezomib plus dexamethasone (Vd) alone (CASTOR) and D-Rd vs Rd alone (POLLUX) in patients with relapsed and refractory multiple myeloma (RRMM). In the pooled intent-to-treat (ITT) population of CASTOR and POLLUX, PFS benefit of the DARZALEX (median, 24.2 months) vs control (median, 7.5 months) arm was observed (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.290.52) and overall survival (OS) benefit of the DARZALEX (median, 50.8 months) vs control (median, 28.8 months) arm was observed (HR, 0.65; 95% CI, 0.49-0.86) in patients with renal impairment. PFS benefit of the DARZALEX vs control arm was observed in patients with renal impairment in the ITT populations of each of the CASTOR and POLLUX studies.
  • Other relevant literature has been identified in addition to the data summarized above.6,7

PRODUCT LABELING

clinical Data

Analysis of Clinically Important Subgroups in the MAIA Study

Moreau et al (2025)3 presented the efficacy and safety results in clinically important subgroups of patients with NDMM from the MAIA study.

Study Design/Methods

  • Efficacy outcomes (PFS, ORR, and MRD-negativity) were analyzed in subgroups based on renal insufficiency (baseline CrCl ≤60 mL/min).3

Results

Patient Characteristics
  • Overall, 737 (D-Rd, n=368; Rd, n=369) patients were included in the ITT population, of whom 162 patients in the D-Rd arm and 142 patients in the Rd arm had renal insufficiency.3
  • The median follow-up was 64.5 months.3
Efficacy

Subgroup Analysis of PFS in the ITT Population of MAIA3
Subgroup
D-Rd
Rd
HR (95% CI)a
n/N
Median PFS, Month
n/N
Median PFS, Month
ITT (overall)
176/368
61.9
228/369
34.4
0.55 (0.45-0.67)
Patient characteristics
   Renal insufficiency
82/162
56.7
92/142
29.7
0.55 (0.41-0.75)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HR, hazard ratio; ITT, intent-to-treat; PFS, progression-free survival; Rd, lenalidomide + dexamethasone.
aHR <1 indicates an advantage for D-Rd.

Subgroup Analysis of ORR in the ITT Population of MAIA3
Subgroup
D-Rd
n/N (%)
Rd
n/N (%)
OR (95% CI)a
ITT (overall)
342/368 (92.9)
301/369 (81.6)
2.97 (1.84-4.79)
Patient characteristics
   Renal insufficiency
146/162 (90.1)
112/142 (78.9)
2.44 (1.27-4.70)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; ITT, intent-to-treat; OR, odds ratio; ORR, overall response rate; Rd, lenalidomide + dexamethasone.
aOR >1 indicates an advantage for D-Rd.

Subgroup Analysis of MRD-Negativity (10-5) Rates in the ITT Population of MAIA3
Subgroup
D-Rd
n/N (%)
Rd
n/N (%)
OR (95% CI)a
ITT (overall)
118/368 (32.1)
41/369 (11.1)
3.78 (2.55-5.59)
Patient characteristic
   Renal insufficiency
48/162 (29.6)
11/142 (7.7)
5.01 (2.49-10.11)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; ITT, intent-to-treat; MRD, minimal residual disease; OR, odds ratio; Rd, lenalidomide + dexamethasone.
aOR >1 indicates an advantage for D-Rd.

Subgroup Analysis of Rates of Sustained MRD-Negativity (10-5) Lasting ≥12 Months in the ITT Population3
Subgroup
D-Rd
n/N (%)
Rd
n/N (%)
OR (95% CI)a
ITT (overall)
69/368 (18.8)
15/369 (4.1)
5.45 (3.05-9.72)
Patient characteristic
   Renal insufficiency
30/162 (18.5)
2/142 (1.4)
15.91 (3.73-67.89)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; ITT, intent-to-treat; MRD, minimal residual disease; OR, odds ratio; Rd, lenalidomide + dexamethasone.
aOR >1 indicates an advantage for D-Rd.
Safety (Patients Aged ≥75 Years)
  • Among patients aged ≥75 years, grade 3/4 TEAEs were reported in 95.5% vs 95.0% of patients in the D-Rd vs Rd arm.3
  • Serious TEAEs were reported in 80.9% vs 79.2% of patients in the D-Rd vs Rd arm, the most common of which was pneumonia (D-Rd, 19.7%; Rd, 12.6%).3
  • TEAEs led to treatment discontinuation in 15.3% vs 27.7% of patients in the D-Rd vs Rd arm.3
  • TEAEs resulting in death were reported in 11.5% vs 13.2% of patients in the D-Rd vs Rd arm.3

Most Common (≥10%) Grade 3/4 TEAEs Among Patients Aged ≥75 Years in the Safety Population3
Grade 3/4 TEAEs, n (%)
D-Rd
(n=157)
Rd
(n=159)
Neutropenia
98 (62.4)
66 (41.5)
Lymphopenia
33 (21.0)
20 (12.6)
Anemia
32 (20.4)
40 (25.2)
Pneumonia
32 (20.4)
23 (14.5)
Leukopenia
19 (12.1)
12 (7.5)
Hypokalemia
18 (11.5)
17 (10.7)
Hypertension
17 (10.8)
8 (5.0)
Thrombocytopenia
16 (10.2)
19 (11.9)
Diarrhea
16 (10.2)
8 (5.0)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event.

Subgroup Analysis of Patients with Renal Impairment and/or High Cytogenetic Risk in the MAIA Study

Facon et al (2022)4 conducted a subgroup analysis of the phase 3 MAIA study that evaluated the efficacy and PROs of D-Rd vs Rd in subgroups of patients with NDMM who had renal impairment (CrCl ≤60 mL/min) and/or high-risk cytogenetics. Results of a subgroup of patients based on renal function are summarized below.

Study Design/Methods

  • Renal impairment was defined as CrCl ≤60 mL/min.4
  • Patients with high cytogenetic risk had a del17p, t(4;14), or t(14;16) abnormality.4

Results

Patient Characteristics
  • Overall, 368 and 369 patients were randomized to the D-Rd and Rd arms, respectively. Baseline renal function status in the ITT population is summarized in Table: Baseline Renal Function.4

Baseline Renal Function4
Characteristic
D-Rd (n=368)
Rd (n=369)
Baseline renal function (CrCl), n (%)
   >60 mL/min
206 (56.0)
227 (61.5)
   ≤60 mL/min
162 (44.0)
142 (38.5)
Abbreviations: CrCl, creatinine clearance; D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone.
Efficacy

Efficacy Outcomes in the Overall Study Population and in Renal Function Subgroup4
Parameter
D-Rd
Rd
HR (95% CI)
P Value
Median time to ≥VGPR, monthsa,b
   ITT population
3.8
9.4
2.08 (1.73-2.49)
<0.0001
   Renal function
      CrCl ≤60 mL/min
3.8
12.5
2.26 (1.69-3.02)
<0.0001
      CrCl >60 mL/min
3.8
8.5
1.82 (1.45-2.28)
<0.0001
Median time to ≥CR, months
   Renal function
      CrCl ≤60 mL/min
23.3
54.6
1.58 (1.07-2.33)
0.0197
      CrCl >60 mL/min
17.6
43.8
1.80 (1.34-2.41)
<0.0001
48-month EFS rate in patients achieving ≥CR, %
   ITT populationc,d
81.8
57.8
0.38 (0.23-0.65)
0.0002
   Renal function
      CrCl ≤60 mL/min
81.0
61.5
0.45 (0.20-1.04)
0.0551
      CrCl >60 mL/min
82.2
55.3
0.41 (0.22-0.77)
0.0043
48-month EFS rate in patients achieving ≥PR, %
   Renal function
      CrCl ≤60 mL/min
67.2
44.4
0.50 (0.34-0.74)
0.0003
      CrCl >60 mL/min
69.8
48.9
0.50 (0.36-0.70)
<0.0001
Abbreviations: CI, confidence interval; CR, complete response; CrCl, creatinine clearance; D-Rd, DARZALEX + lenalidomide + dexamethasone; EFS, event-free survival; HR, hazard ratio; ISS, International Staging System; ITT, intent-to-treat; PR, partial response; Rd, lenalidomide + dexamethasone; VGPR, very good partial response.
aHR and 95% CI are calculated from a Cox proportional hazards model, with treatment as the sole explanatory variable. HR >1 indicates an advantage for D-Rd.
bP value was based on the log-rank test.
cHR and 95% CI are calculated from a Cox proportional hazards model, with treatment as the sole explanatory variable and stratified by ISS stage (I, II, or III), region (North America vs other), and age (<75 years vs ≥75 years), as randomized. HR <1 indicates an advantage for D-Rd.
dP value was based on a stratified log-rank test.

Post Hoc Analysis of Clinically Relevant Subgroups in the CASTOR and POLLUX Studies

Mateos et al (2022)5 presented a post hoc analysis of the phase 3 CASTOR and POLLUX studies to evaluate the efficacy of D-Vd vs Vd and D-Rd vs Rd in subgroups of patients with RRMM. Results of a subgroup of patients with renal impairment (CrCl ≤60 mL/min) are summarized below.

Study Design/Methods

  • Patients were randomized to receive D-Vd or Vd in CASTOR and D-Rd or Rd in POLLUX.5
  • Primary endpoint: PFS5
  • The efficacy outcomes were compared between treatment arms according to subgroups, including renal impairment (CrCl ≤60 mL/min).5

Results

Patient Characteristics

PFS and OS in the Pooled ITT Population from CASTOR and POLLUX5
Subgroup
PFS
OS
DARZALEX
Arm
Control
Arm
HR
(95%
CI)
DARZALEX Arm
Control
Arm
HR
(95% CI)
n/N
Median, Mos
n/N
Median, Mos
n/N
Median, Mos
n/N
Median, Mos
Renal impairmenta
101/137
24.2
114/135
7.5
0.39
(0.29-0.52)
88/137
50.8
104/135
28.8
0.65
(0.49-0.86)
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; HR, hazard ratio; ITT, intent-to-treat; Mos, months; OS, overall survival; PFS, progression-free survival.aRenal impairment was defined as baseline CrCl ≤60 mL/min.

PFS in the ITT Population of CASTOR5
Subgroup
D-Vd
Vd
HR (95% CI)
P Value
n/N
Median, Months
n/N
Median, Months
Renal impairment
45/57
13.1
61/70
6.2
0.32 (0.20-0.50)
<0.0001
Abbreviations: CI, confidence interval; DVd, DARZALEX + bortezomib + dexamethasone; HR, hazard ratio; ITT, intent-to-treat; PFS, progression-free survival; Vd, bortezomib + dexamethasone.

PFS in the ITT Population of POLLUX5
Subgroup
D-Rd
Rd
HR (95% CI)
P Value
n/N
Median, Months
n/N
Median, Months
Renal impairment
56/80
33.6
53/65
11.3
0.42 (0.28-0.62)
<0.0001
Abbreviations: CI, confidence interval; DRd, DARZALEX + lenalidomide + dexamethasone; HR, hazard ratio; ITT, intent-to-treat; PFS, progression-free survival; Rd, lenalidomide + dexamethasone.

ORR and MRD-Negativity (10-5) Rates in CASTOR5
Subgroup
ORRa
MRD-Negativity Rateb
D-Vd,
n/N (%)
Vd,
n/N (%)
OR
(95% CI)
P Value
D-Vd,
n/N (%)
Vd,
n/N (%)
OR
(95% CI)
P Value
Renal impairmente
44/56 (78.6)
39/68 (57.4)
2.73
(1.23-6.06)
0.0128
3/57
(5.3)
0/70
NE
(NE-NE)
0.0878
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; DVd, DARZALEX + bortezomib + dexamethasone; MRD, minimal residual disease; NE, not estimable; OR, odds ratio; ORR, overall response rate; Vd, bortezomib + dexamethasone.aRenal impairment was defined as baseline CrCl ≤60 mL/min.

ORR and MRD-Negativity (10-5) Rates in POLLUX5
Subgroup
ORRa
MRD-Negativity Rateb
D-Rd,
n/N (%)
Rd,
n/N (%)
OR
(95% CI)
P Value
D-Rd,
n/N (%)
Rd,
n/N (%)
OR
(95% CI)
P Value
Renal impairmenta
73/80 (91.3)
43/63 (68.3)
4.85
(1.90-12.41)
0.0005
24/80 (30.0)
4/65
(6.2)
6.54
(2.13-20.01)
0.0003
Abbreviations: CI, confidence interval; DRd, DARZALEX + lenalidomide + dexamethasone; MRD, minimal residual disease; NE, not estimable; OR, odds ratio; ORR, overall response rate; Rd, lenalidomide + dexamethasone.aRenal impairment was defined as baseline CrCl ≤60 mL/min.

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
24 March 2026. For streamlining purposes, retrospective analysis, systematic reviews, review articles, and case reports have been excluded.

 

References

Show
1 Data on File. Daratumumab IV Company Core Data Sheet (CCDS). Janssen Research & Development, LLC. EDMS-ERI-78724630; 2026.  
2 Data on File. Daratumumab SC Company Core Data Sheet (CCDS). Janssen Research & Development, LLC. EDMS-ERI-184804517; 2026.  
3 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.  
4 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.  
5 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. Poster presented at: 19th International Myeloma Society (IMS) Annual Meeting; August 25-27, 2022; Los Angeles, CA.  
6 Usmani S, Kumar S, Plesner T, et al. Efficacy of daratumumab, lenalidomide, and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma and impaired renal function from the phase 3 MAIA study based on lenalidomide starting dose. Poster presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual Meeting.  
7 Harvey R, Franz J, Joseph N, et al. Phase 2 evaluation of daratumumab-based induction therapy in multiple myeloma patients with severe renal insufficiency. Poster presented at: Amercian Society of Clinical Oncology (ASCO) Annual Meeting; June 2-6, 2023; Chicago, IL.