SUMMARY  

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• There is no systemically collected data on the management of infections with DARZALEX/DARZALEX FASPRO treatment. Clinical judgement should be exercised when managing infections during DARZALEX/DARZALEX FASPRO containing treatment regimens.
• CASTOR: phase 3 study evaluating the safety and efficacy of bortezomib and dexamethasone (Vd) alone and DARZALEX for intravenous (IV) use in combination with Vd (D-Vd).^1,2 The most common infection-related any grade treatment-related adverse event (TEAE) was upper respiratory tract infection (URTI; D-Vd, 37.0%; Vd, 18.1%) (TEAE; any grade).²
• CANDOR: 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 RRMM.³ The most common infection-related any grade TEAE was URTI (D-Kd, 34.1%; Kd, 24.2%).⁴
• POLLUX: phase 3 study evaluating the safety and efficacy of lenalidomide and dexamethasone (Rd) vs DARZALEX in combination with Rd (D-Rd).^5,6 In the D-Rd vs Rd arm, grade 3/4 infections were reported in 44.5% vs 28.1% patients. The most common infection-related TEAE (any grade) was URTI (D-Rd, 44.2%; Rd, 28.1%).⁶
• Usmani et al (2020)⁷ reported the final results from a pooled, post-hoc analysis from the phase 2 DARZALEX monotherapy studies, GEN501 and SIRIUS. Most URTIs were reported as grade 1/2 (22%, n=32) in this pooled analysis.
• EQUULEUS: phase 1b study evaluating DARZALEX in various standard-of-care regimens in patients with multiple myeloma (MM) and those who received prior treatment.^8,9
  • Chari et al (2017)⁸ reported safety and tolerability results of the DARZALEX in combination with pomalidomide and dexamethasone (D-Pd) arm for patients with RRMM. The most common infection-related TEAE (any grade) was URTI (D-Pd, 28%).
  • Moreau et al (2023)⁹ reported the final results from the D-Kd arm of the PLEIADES and EQUULEUS studies at a median follow-up of 12.4 and 23.7 months, respectively. The most common infection-related TEAE (any grade) was URTI (D-Kd, 44.7%). Results specific to the D-Kd arm of the EQUULEUS study have been summarized below.
• GEN503: phase 1/2, dose escalation and dose expansion study assessing the safety and efficacy of DARZALEX with Rd. URTI (D-Rd, 25%) was the most common infection-related TEAE (any grade).¹⁰
• COLUMBA: phase 3 study evaluating the efficacy, pharmacokinetics (PK), and infusion-related reactions (IRRs) of DARZALEX vs DARZALEX FASPRO for subcutaneous (SC) use.^11,12 URTI (DARZALEX, 11.6%; DARZALEX FASPRO, 16.9%) was the most common infection-related TEAE (any grade). ¹²
• APOLLO: phase 3 study evaluating the safety and efficacy of daratumumab in combination with pomalidomide and dexamethasone (Pd) vs Pd alone in patients with RRMM who received ≥1 prior treatment with both lenalidomide and a proteasome inhibitor.^13,14 The most common infection-related TEAE (any grade) was URTI (D-Pd, 24.8%; Pd, 16%).¹⁴
• PLEIADES: phase 2 study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with 4 standard-of-care treatment regimens, specifically, in combination with Rd in patients with RRMM with ≥1 prior line of therapy (≥1PL) and in combination with Kd in patients with RRMM with 1PL.^9,15
  • Moreau et al (2020)¹⁵ presented the primary analysis of the D-Kd arm with a median follow-up of 9.2 months and the updated safety and efficacy results of the D-Rd arm with a median follow-up of 25.7 months. Pneumonia was the most common infection-related TEAE (D-Kd, 3%; D-Rd, 15%).
  • Moreau et al (2023)⁹ reported the final results from the D-Kd arm of the PLEIADES and EQUULEUS studies at a median follow-up of 12.4 and 23.7 months, respectively. The most common infection-related TEAE (any grade) was nasopharyngitis (D-Kd, 25.8%). Results specific to the D-Kd arm of the PLEIADES study have been summarized below.
• PAVO: phase 1b, dose-finding, proof-of-concept study evaluating the safety, PK, and efficacy of a mixed formulation of daratumumab and recombinant human hyaluronidase PH20 (rHuPH20; daratumumab-MD) and DARZALEX FASPRO in patients with RRMM who have received ≥2 prior therapies.¹⁶
  • All-grade infection-related TEAE was URTI in part 1 (1200 mg group, 38%; 1800 mg group, 24%) and part 2 (DARZALEX FASPRO, 8%).¹⁶
  • In the updated results from part 2, the most common all-grade infection-related TEAEs was nasopharyngitis (24%).¹⁷
  • In the updated results from part 3, the most common all-grade infection-related TEAE was URTI (3-week corticosteroid taper group, 40.0%; 2-week corticosteroid taper group, 20.0%; 1week corticosteroid taper group, 8.3%).¹⁸

PRODUCT LABELING

• DARZALEX (daratumumab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.

CLINICAL DATA - RELAPSED AFTER ≥1 PRIOR THERAPY

DARZALEX in Combination with Bortezomib and Dexamethasone

CASTOR (MMY3004; NCT02136134) is a phase 3 study which evaluated the safety and efficacy of Vd alone compared to D-Vd in patients with RRMM (N=498).^1,2 Sonneveld et al (2023)² published the updated safety and efficacy results at a median follow-up of 72.6 months. Safety results related to infections have been summarized below.

Safety Results - Infection-Related

• Infection-related TEAEs are summarized in Table: Any Grade or Grade 3/4 Infection-Related TEAEs (CASTOR).
• The most common serious TEAE was pneumonia (D-Vd, 10.7%; Vd, 10.1%).
• Treatment discontinuation due to infections was reported in 7 (2.9%) patients in the D-Vd arm and 5 (2.1%) patients in the Vd arm.
• Pneumonia was reported as the most frequent TEAE (0.8% in both arms) with an outcome of death in the D-Vd arm.
• Three deaths occurred due to COVID-19 disease (D-Vd, n=1; Vd, n=2).

DARZALEX in Combination with Carfilzomib and Dexamethasone  

CANDOR (NCT03158688) is an ongoing, randomized, open-label, multicenter, phase 3 study evaluating the efficacy and safety of D-Kd vs Kd in patients with RRMM.^3,4 Usmani et al (2023)⁴ reported final analysis of the CANDOR study after a median follow-up of 50 months. Safety results related to infections have been summarized below.

Safety Results - Infection-Related

• The most common infection-related TEAEs are presented in Table: Most Common Any Grade (≥20%) and Grade ≥3 (≥5%) Infection-Related TEAEs and TEAEs of Interest (CANDOR).
• Grade ≥3 TEAEs occurred in 273 (89%) vs 120 (78%) patients in the D-Kd vs Kd arm, with the most common infection-related TEAE in both groups being pneumonia.
• Grade ≥3 infections and infestations occurred in 46% (n=142) vs 32% (n=49) patients in the D-Kd vs Kd arm and led to carfilzomib discontinuation in 22% (n=69) vs 20% (n=30) patients.
• Fatal TEAEs occurred in 35 (11%) vs 9 (6%) patients in the D-Kd vs Kd arm; the most common fatal TEAE was infection (D-Kd, n=21 [7%]; Kd, n=5 [3%]). See Table: Infection-Related Fatal TEAEs.
• Three patients reported treatment-related fatal AEs related to infection in the D-Kd arm only (Acinetobacter infection, pneumonia, and sepsis [n=1 each]). Fatal infection rates were 7% (n=21) vs 3% (n=5) in the DKd vs Kd arm; correspondingly, when adjusted for exposure, fatal infection rates were 3.5 vs 2.55 per 100 patient-years.
• TEAEs related to COVID-19 occurred in 11% (n=33) vs 4% (n=6) patients in the D-Kd vs Kd arm, and deaths related to COVID-19 occurred in 2% (n=6) vs 1% (n=1) patient.

DARZALEX in Combination with Lenalidomide and Dexamethasone

POLLUX (MMY3003; NCT02076009) is a randomized, open-label, active-controlled (Rd arm), multicenter, phase 3 study that evaluated the safety and efficacy of Rd and D-Rd in patients with RRMM (N=569).^5,6 Dimopoulos et al (2023)⁶ reported the updated safety and efficacy results of the POLLUX study at a median follow-up of 79.7 months. Safety results related to infections have been summarized below.

Safety Results - Infection-Related

• Infection-related TEAEs are summarized in Table: Any Grade or Grade 3/4 Infection-Related TEAEs (POLLUX).
• In the D-Rd vs Rd arm, grade 3/4 infections were reported in 126 (44.5%) vs 79 (28.1%) patients and treatment discontinuation due to infections was reported in 13 (4.6%) vs 11 (3.9%) patients.
• In the D-Rd vs Rd arm, the most common TEAEs resulting in death included septic shock (1.4% vs 0.4%) and pneumonia (0.7% vs 1.1%).

DARZALEX FASPRO in Combination with Pomalidomide and Dexamethasone

APOLLO (MMY3013; NCT03180736) is an ongoing, phase 3 study evaluating the safety and efficacy of D-Pd vs Pd in patients with RRMM who received ≥1 prior treatment with both lenalidomide and a proteasome inhibitor (N=304).¹³ Dimopoulos et al (2022)¹⁴ presented the updated safety analysis at a median follow-up of 39.6 months. Safety results related to infections have been summarized below.

Safety Results - Infection-Related

• For information regarding infection-related TEAEs, see Table: Most Common Any Grade (≥15%) and Grade 3/4 (≥5%) Infection-Related TEAEs in the Safety Population (APOLLO).
• Treatment discontinuation due to infections was reported in 1 (0.7%) patient in both arms.
• TEAEs resulting in deaths due to COVID-19 were reported in 1.3% (n=2) vs 0.7% (n=1) patients in the D-Pd vs Pd arm.
• The most common serious TEAEs (>10%) were pneumonia (D-Pd, 15.4%; Pd, 8.7%) and lower respiratory tract infection (D-Pd, 12.1%; Pd, 9.3%).

DARZALEX FASPRO in Combination with 4 Standard-of-Care Regimens

PLEIADES (MMY2040; NCT03412565) is an ongoing, phase 2, non-randomized, open-label, multicenter study evaluating the clinical benefit of DARZALEX FASPRO when administered in combination with 4 standard-of-care treatment regimens in patients with MM.^9,15Moreau et al (2023)⁹ reported the final results from the D-Kd arm of the PLEIADES and EQUULEUS studies. Safety results related to infections in the D-Kd and D-Rd arms have been summarized below.

Safety Results - Hematologic Adverse Events - D-Kd (Final Results)

• Grade 3/4 infections were reported in 9 (13.6%) patients, the most common being pneumonia (4.5%).⁹
• For information regarding infection-related TEAEs, see Table: Most Common Infection-Related Any Grade (≥25%) and Grade 3/4 (≥5%) TEAEs in the D-Kd arm (PLEIADES).⁹
• Serious TEAEs were reported in 22 (33.3%) patients, the most common being pneumonia (4.5%).⁹
• Grade 5 TEAEs were reported in 3 patients (COVID-19 pneumonia, sepsis, and respiratory failure; 1 patient each).⁹

clinical data - Relapsed/Refractory or Double Refractory

DARZALEX vs DARZALEX FASPRO Non-Inferiority Study

COLUMBA (MMY3012; NCT03277105) is an ongoing, phase 3, randomized, open-label, multicenter, non-inferiority study evaluating the efficacy, PK, and IRRs of DARZALEX vs DARZALEX FASPRO in patients with RRMM.^11,12 Usmani et al (2022)¹² reported final analysis of efficacy and safety results of the COLUMBA study after a median follow-up of 29.3 months. Safety results related to infections have been summarized below.

Safety Results - Infection-Related

• TEAEs-related to infection are summarized in Table: Most Common Any Grade (≥10%) and Grade 3/4 (≥5%) Infection-Related TEAEs in the Safety-Evaluable Population (COLUMBA).
• The most common serious adverse event (SAE) was pneumonia (DARZALEX FASPRO, 4.6% [n=12]; DARZALEX, 5% [n=13]).
• With the longer follow-up, the rates of any grade and grade 3/4 TEAEs across all body weight subgroups (≤65 Kg, >65-85 kg, and >85 kg) were similar to the overall population. See Table: Most Common Grade 3/4 (≥5%) Infection-Related TEAEs Across Body Weight Subgroups (COLUMBA).
  • In the ≤65 kg subgroup, there was no increase in the incidence of infections for any grade TEAEs (DARZALEX FASPRO, 57.0%; DARZALEX, 57.6%), and grade 3/4 TEAEs (DARZALEX FASPRO, 10.8%; DARZALEX, 17.4%).
  • In the ≤65 kg subgroup, incidence of serious infections was 10.8% vs 18.5% in the DARZALEX FASPRO vs DARZALEX arms, respectively.

DARZALEX in Combination with Pomalidomide and Dexamethasone

EQUULEUS (MMY1001; NCT01998971) is a phase 1b, open label, non-randomized, multicenter study evaluating the safety, tolerability, and dose regimen of DARZALEX in combination with various backbone treatment regimens for the treatment of patients with MM. Moreau et al (2023)⁹ reported the final results from the D-Kd arm of the PLEIADES and EQUULEUS studies at a median follow-up of 12.4 and 23.7 months, respectively. Safety results related to infections in the D-Pd and D-Kd arms have been summarized below.

Safety Results - Infection-Related - D-Kd arm (Final Results)

• Grade 3/4 infections occurred in 18 (21.2%) patients, the most common being pneumonia (4.7%).⁹
• For information regarding infection-related TEAEs, see Table: Most Common Infection-Related Any Grade (≥25%) and Grade 3/4 (≥5%) TEAEs in the D-Kd arm (EQUULEUS).⁹
• The most common serious TEAEs were pneumonia and URTI (4.7% each)⁹

DARZALEX Dose Escalation, Dose Expansion Study in Combination with Rd

Plesner et al (2019)¹⁰ reported final results from GEN503, a dose escalation and dose expansion study assessing the safety and efficacy of D-Rd in patients with RRMM (N=32). Safety results related to infections have been summarized below.

Safety Results - Infection-Related

• In part 2, two deaths were reported due to viral pneumonia and Epstein-Barr virus association (n=1 each).
• For information regarding infection-related TEAEs, see Table: Most Common (≥25%) Infection-Related TEAEs in Part 2 of GEN503 Study.

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
25 June 2025. For streamlining purposes, retrospective-analyses, systematic reviews, review articles, and case reports have been excluded.

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