DARZALEX + DARZALEX FASPRO - Infections in Patients with Newly Diagnosed Multiple Myeloma

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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• There is no systematically collected data on the management of infections with DARZALEX/DARZALEX FASPRO treatment. Clinical judgment should be exercised when managing infections during DARZALEX/DARZALEX FASPRO-containing treatment regimens.
• Johnson & Johnson does not recommend the use of DARZALEX/DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.

Transplant-Eligible Newly Diagnosed Multiple Myeloma

• CASSIOPEIA is a phase 3 study evaluating the safety and efficacy of DARZALEX for intravenous (IV) use in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) in transplant eligible patients with previously untreated multiple myeloma (MM).¹
  • Part 1: Moreau et al (2019)¹ reported results from Part 1 of the CASSIOPEIA study. Infections of any grade were an adverse event (AE) of interest. In the D-VTd arm vs bortezomib, thalidomide, and dexamethasone (VTd) arm, any grade infections were reported in 65% vs 57% of patients, and grade 3/4 infections were reported in 22% vs 20% of patients.
  • Part 2: Moreau et al (2021)^2,3 reported results from Part 2 of the CASSIOPEIA study. Infections occurred in 77.5% of patients in the DARZALEX monotherapy arm vs 64% in the observation arm.
• GRIFFIN is a phase 2, 2-part study evaluating the safety and efficacy of DARZALEX when administered in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) in patients with newly diagnosed multiple myeloma (NDMM) eligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT).^4-6
  • Part 1: Voorhees et al (2021)⁷ reported the final analysis of the safety run-in cohort of the GRIFFIN study with a median follow-up of 40.8 months. Fourteen patients (87.5%) experienced any grade infections, and 5 patients (31.3%) experienced grade 3/4 infections.
  • Part 2: Voorhees et al (2023)⁸ reported the final analysis results of the GRIFFIN study after all patients completed ≥1 year of long-term follow-up after the end-of-study treatment, death, or withdrawal. The median follow-up was 49.6 months. In the D-VRd vs VRd arm, any grade infections were reported in 93% vs 66% of patients and grade 3/4 infections were reported in 29% vs 26% of patients, respectively.
• LYRA is a phase 2 study evaluating the safety and efficacy of DARZALEX in combination with cyclophosphamide, dexamethasone, and bortezomib (CyBorD) for the treatment of MM in patients who have not received previous treatment or have relapsed after receiving only 1 line of treatment.^9,10
  • Yimer et al (2022)¹¹ reported the end-of-study analysis of LYRA. In patients with NDMM, the most common grade 3/4 infection-related treatment-emergent adverse event (TEAE) was pneumonia (3.5%).
• PLEIADES is a phase 2 study evaluating the clinical benefit of DARZALEX FASPRO for subcutaneous (SC) use administered in combination with 4 standard-of-care treatment regimens.^12-16
  • Chari et al (2020)¹² presented updated safety and efficacy results of the D-VRd arm for patients with transplant-eligible NDMM in the PLEIADES study (n=67). Pneumonia was reported in 3% of patients in this arm.
• PERSEUS is a phase 3 study evaluating the safety and efficacy of D-VRd vs VRd induction and consolidation followed by maintenance with DARZALEX FASPRO and lenalidomide (D-R) in D-VRd group or lenalidomide (R) in VRd group in patients with NDMM eligible for ASCT.¹⁷
  • Sonneveld et al (2023)¹⁷ reported safety and efficacy results from the PERSEUS study. At a median follow-up of 47.5 months the most common infection-related grade 3/4 AE recorded in the D-VRd vs VRd group was pneumonia (10.5% vs 6.1%).
• MASTER is a phase 2 study evaluating the efficacy and safety of DARZALEX in combination with carfilzomib, lenalidomide, and dexamethasone (D-KRd) in patients with NDMM. The most common serious TEAE was pneumonia (n=8).¹⁸
  • Costa et al (2023)¹⁸ reported the final results of the MASTER study. The most common infection-related TEAE was upper respiratory infection (grade 1/2, 36%).
• Rodriguez-Otero et al (2024)¹⁹ reported results from a post hoc analysis of the PERSEUS and GRIFFIN studies that evaluated the efficacy and safety of D-VRd vs VRd in patients aged ≥65 years. A higher incidence of grade 3/4 infections was observed in the D-VRd vs VRd group, with slightly higher rates in patients aged ≥65 years (36.3% vs 24.8%) than in all patients (29.5% vs 22.5%).

Transplant-Ineligible Newly Diagnosed Multiple Myeloma

• MAIA is a phase 3 study evaluating the safety and efficacy of DARZALEX in combination with lenalidomide and dexamethasone (D-Rd) compared with lenalidomide and dexamethasone (Rd) in transplant-ineligible (TIE) patients with NDMM.²⁰
  • Facon et al (2025)²¹ reported the results of an updated analysis of the MAIA study at a median follow-up of 64.5 months. Grade 3/4 infections occurred in 42.6% vs 29.6% of patients from the D-Rd vs Rd arm, respectively.
  • Facon et al (2024)²² presented the results of an updated analysis of the MAIA study at a median follow-up of 89.3 months. In the D-Rd arm vs Rd arm, deaths due to infections/infestations were reported in 2.5% vs 8.2% of patients.
  • Venner et al (2026)²³ presented the results of an age and frailty analysis of TIE patients in the MAIA and CEPHEUS studies. Infections and infestations were reported across age and frailty subgroups.  
• ALCYONE is a phase 3 study evaluating the safety and efficacy of bortezomib, melphalan, and prednisone (VMP) alone and DARZALEX + VMP (D-VMP) in patients with NDMM who were ineligible for HDT with ASCT.²⁴
  • Mateos et al (2025)²⁵ reported the final efficacy and safety analysis results of the ALCYONE study at a median follow-up of 86.7 months. Pneumonia was the most common grade 3/4 infection, reported by 16% of patients in the D-VMP group and 5% of patients in the VMP group.
• Bahlis et al (2026)²⁶ published a pooled analysis of the MAIA and ALCYONE studies to assess incidence, timing, and management of infection. There was a higher incidence of grade 3/4 infections in the D-Rd/D-VMP arm (36.9%) vs the Rd/VMP arm (22.4%). Across treatment groups, any-grade infection led to treatment discontinuation in approximately 2% of patients.
• PLEIADES is a phase 2 study evaluating the clinical benefit of DARZALEX FASPRO for SC use administered in combination with 4 standard-of-care treatment regimens.^12-16
  • Moreau et al (2020)¹⁶ presented updated safety and efficacy results of the D-VMP arms in the PLEIADES study (n=67). Pneumonia was reported in 7% of patients in the D-VMP arm.
• 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 D-R vs R alone in patients with NDMM who are anti-cluster of differentiation (CD) 38 naïve, have a very good partial response or better (≥VGPR), and are MRD-positive following ASCT after standard-of-care induction/consolidation.^27-29 
  • Anderson et al (2025)²⁹ presented updated efficacy and safety results from the phase 3 AURIGA study at 24 months from the start of maintenance therapy, with a median follow-up of 40.3 months. In the D-R vs R arm, grade 3/4 infections were reported in 19.8% vs 14.3% of patients, respectively. A serious TEAE pneumonia was reported in 5.2% vs 5.1% of patients in the D-R vs R arm, respectively.
  • Foster et al (2024)³⁰ presented a post hoc analysis of the phase 3 AURIGA study that evaluated clinically relevant subgroups at a median follow-up of 32.3 months. 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. D-R maintenance did not increase grade 3/4 infection rates in patients ≥65 years of age.
• CEPHEUS is a phase 3 study evaluating the efficacy and safety of DARZALEX FASPRO in D-VRd or VRd in patients with NDMM who are TIE or for whom transplant is not planned as initial therapy (transplant deferred).³¹
  • Usmani et al (2025)³¹ reported results from the phase 3 CEPHEUS study at a median follow-up of 58.7 months. Serious TEAEs occurred in 72.1% vs 67.2% of patients from the D-VRd vs VRd arm, respectively, with the most common serious TEAE being pneumonia (D-VRd, 13.7%; VRd, 12.8%). Any grade infections occurred in 91.9% vs 85.6% of patients from the D-VRd vs VRd arm, respectively. Grade 3/4 TEAE infections occurred in 40.1% and 31.8% of patients from the D-VRd vs VRd arm, respectively.
  • Venner et al (2026)²³ presented the results of an age and frailty analysis of TIE patients in the MAIA and CEPHEUS studies. Infections and infestations were reported across age and frailty subgroups.  
  • Facon et al (2025)³² presented a post hoc subgroup analysis of the phase 3 CEPHEUS study. The safety outcomes were consistent with the intention-to-treat (ITT) population, with no new safety concerns and a lower rate of grade 5 TEAEs when censored for COVID-19. Additionally, the incidence of grade 3 or 4 TEAEs was 79.9% in the D-VRd group and 79.6% in the VRd group.

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 - transplant-eligible NDMM

DARZALEX in Combination with VTd in Previously Untreated MM

CASSIOPEIA (MMY3006; NCT02541383) is a phase 3, open-label, 2-arm, multicenter study evaluating the safety and efficacy of D-VTd in patients with previously untreated MM who are eligible for HDT and ASCT.¹

Primary Analysis of Part 1 of the CASSIOPEIA Study

Moreau et al (2019)¹ reported the results from Part 1 of this study at a median follow-up of 18.8 months (range, 0.0-32.2). Results specific to infections are summarized below.

Safety Results -  Infection-Related Events in Part 1

• Infections of any grade were an AE of interest. In the D-VTd arm, 65% of patients (n=351) and 57% of patients (n=306) in the VTd arm reported infections of any grade.¹
• Grade 3/4 infections were reported in 22% of patients (n=118) in the D-VTd arm and 20% of patients (n=105) in the VTd arm. See Table: Most Common Infection-Related Adverse Events During Treatment in Safety Population (CASSIOPEIA Part 1).¹
• Six patients discontinued DARZALEX treatment due to TEAEs of infections.¹
• Among the most common serious adverse events (SAEs; ≥3% of patients in either arm), pneumonia was reported in 4% (n=19) in the D-VTd arm and 2% (n=9) in the VTd arm.¹
• A total of 14 deaths were reported in the D-VTd arm and 32 in the VTd arm. Septic shock was reported as a cause of death (n=1) in the VTd arm.³³

Primary Analysis of Part 2 of the CASSIOPEIA Study

Moreau et al (2021)^2,3 reported the results from Part 2 of the CASSIOPEIA study (maintenance treatment) at a median follow-up of 35.4 months. Results specific to infections are summarized below.

Safety Results -  Infection-Related Events in Part 2

• Infections occurred in 77.5% of patients (n=341) in the DARZALEX monotherapy arm vs 64% of patients (n=284) in the observation arm.³
  • DARZALEX monotherapy arm vs observation arm had a greater incidence of pneumonia (n=29 [6.6%] vs n=19 [4.3%]) and lung infections (n=21 [4.8%] vs n=15 [3.4%]).
• Most infections were grade 1/2 (DARZALEX monotherapy arm, 303 of 331 [88.9%]; observation arm, 254 of 284 [89.4%]).³
• See Table: Most Common Infection-Related AEs during Treatment/Observation in Maintenance-Specific Safety Population (CASSIOPEIA Part 2).²

• SAEs that occurred in >1% of patients in the DARZALEX monotherapy vs observation arms were pneumonia (n=11 [3%] vs n=7 [2%]) and lung infection (n=6 [1%] vs n=7 [2%]), respectively.²
• Two AEs led to death in the DARZALEX monotherapy arm (septic shock and natural killer-cell lymphoblastic lymphoma, n=1 each); both were treatment-related.²

Phase 2 Study of DARZALEX in Combination with VRd in TE NDMM

GRIFFIN (MMY2004; NCT02874742) is a 2-part, phase 2, randomized, active-controlled study evaluating the safety and efficacy of DARZALEX in combination with VRd in patients with NDMM eligible for HDT and ASCT.^4-6

Final Analysis of Part 1 (Safety Run-in Phase) of the GRIFFIN Study

Voorhees et al (2021)⁷ reported the final analysis of the safety run-in cohort (Part 1) of the GRIFFIN study. Results specific to infections are summarized below.

Safety Results - Infection-Related Events in Part 1

• During cycle 1, 3 of 16 patients developed 4 dose-limiting toxicities (DLTs): fatigue, gastroenteritis, hypotension, and pneumonitis.⁷
  • All DLTs were grade 3 and none resulted in treatment discontinuation during induction or consolidation therapy.
• Fourteen patients (87.5%) experienced any grade infections, and 5 patients (31.3%) experienced grade 3/4 infections.⁷
  • During the maintenance phase 31.3% of patients (n=5) experienced any grade infections. The most common being upper respiratory tract infections. One patient (6.3%) experienced 2 grade 3/4 infections (pneumonia and bronchitis).
• Pneumonia was the most common grade 3/4 infection-related TEAE reported in 5 patients (31.3%).⁷

Final Analysis of Part 2 (Randomized Phase) of the GRIFFIN Study

Voorhees et al (2023)⁸ reported the final efficacy and safety results at a median follow-up of 49.6 months after all patients completed ≥1 year of follow-up after the end-of-study treatment, died, or withdrew from study participation. Results specific to infections are summarized below.

Safety Results - Infection-Related Events in Part 2

• Any grade infections were more common in the D-VRd vs VRd arm (93% [n=92] vs 66% [n=67]). Similar incidence rates were reported across treatment arms for grade 3/4 infections (D-VRd, 29%; VRd, 26%) and infections leading to treatment discontinuation (D-VRd, 2%; VRd, 3%).⁸
  • During maintenance therapy (cycle 7+) in the D-VRd vs VRd arm, any grade infections occurred in 35% (n/N=31/89) vs 32% (n/N=23/71) of patients, respectively, and grade 3/4 infections occurred in 18% (n=16) vs 21% (n=15) of patients, respectively.
  • In the D-VRd vs VRd arm, COVID-19 infections were reported in 5% (n=5) vs 2% (n=2) of patients, respectively. Of these, 1 patient in each arm had a grade 3 COVID-19-related event (including 1 serious event in the D-VRd arm).
• Pneumonia was the most common infection-related serious TEAE (D-VRd, 15%; VRd, 14%).⁸
• For the incidence of most common infection-related TEAEs by grade in the safety population, see Table: Most Common Infection-Related TEAEs in the Safety Population (GRIFFIN).⁸

Phase 2 Study of DARZALEX in Combination with CyBorD in MM

LYRA (NCT02951819) is a phase 2, single-arm, open-label, multicenter study evaluating the safety and efficacy of DARZALEX in combination with CyBorD for the treatment of MM in patients who had not received previous treatment or had relapsed after receiving only 1 line of treatment.^9,10

Final Analysis of the LYRA Study

Yimer et al (2022)¹¹ reported the end-of-study analysis results of the LYRA study. Results specific to infections are summarized below.

Safety Results - Infection-Related Events in Patients with NDMM

• The most common serious TEAE was pneumonia (2.3%).¹¹
• For the incidence of most common any grade and grade 3/4 infection-related TEAEs during induction phase, see Table: Most Common Infection-Related TEAEs in the Safety Analysis Set (Induction Phase; LYRA).¹¹

• For the incidence of most common any grade and grade 3/4 infection-related TEAEs during maintenance phase, see Table: Most Common Infection-Related TEAEs in the Safety Analysis Set (Maintenance Phase; LYRA).¹¹

Phase 3 Study of DARZALEX FASPRO in Combination with VRd in TE NDMM

PERSEUS (MMY3014; NCT03710603) is a phase 3, open-label, multicenter study evaluating the efficacy and safety of D-VRd vs VRd induction and consolidation followed by maintenance with D-R in D-VRd group or lenalidomide in VRd group in patients with NDMM eligible for ASCT.¹⁷

Primary Analysis of the PERSEUS Study

Sonneveld et al (2023)¹⁷ reported efficacy and safety results from the PERSEUS study evaluating D-VRd vs VRd in patients with NDMM eligible for ASCT. Results specific to infections are summarized below.

Safety Results - Infection-Related Events 

• The most common infection-related grade 3/4 AE recorded in the D-VRd vs VRd group was pneumonia (10.5% vs 6.1%).¹⁷
• The number of deaths recorded due to COVID-19 in the D-VRd vs VRd group was 4 (1.1%) vs 1 (0.3%) patients, respectively.¹⁷ 
• For the incidence of most common infection-related AEs by grade, see Table: Most Common Infection-Related AEs (PERSEUS).¹⁷

• Serious AEs occurred in 57.0% vs 49.3% of patients in the D-VRd vs VRd arms, respectively. The most common SAEs (occurring in ≥2% of patients in either group) included³⁴: 
  • Infections: 35.0% (D-VRd) vs 27.4% (VRd) 
    • Includes pneumonia, COVID-19, COVID-19 pneumonia, lower respiratory tract infection, sepsis, and upper respiratory tract infection.  

Phase 2 Study of DARZALEX in Combination with KRd in NDMM

MASTER (NCT03224507) was a phase 2, single-arm, open-label, multicenter study evaluating the efficacy and safety of D-KRd in patients with NDMM.¹⁸

Final Analysis of the MASTER Study

Costa et al (2023)¹⁸ reported the final analysis results of the MASTER study. Results specific to infections are summarized below.

Results - Safety - Infection-Related Events

• The most common serious TEAE was pneumonia (n=8).¹⁸
• One patient died during protocol-directed therapy from metapneumovirus pneumonia, which was considered as not related to study treatment.¹⁸
• One patient died after therapy and while on MRD surveillance without disease progression from COVID-19 pneumonia.¹⁸
• For the incidence of most common infection-related TEAEs by grade, see Table: Most Common Infection-Related TEAEs (MASTER).¹⁸

CLINICAL DATA - TRANSPLANT – INELIGIBLE NDMM

Phase 3 Study of DARZALEX in Combination with Rd in TIE NDMM

MAIA (MMY3008; NCT02252172) is a phase 3, randomized, open-label, active-controlled, multicenter study in patients with NDMM not eligible for HDT and ASCT (N=737).²⁰

Age and Frailty Analysis of the MAIA Study

Venner et al (2026)²³ presented the results of an age and frailty analysis of TIE patients in the MAIA and CEPHEUS studies. Results specific to infections in the MAIA study are summarized below.

Safety Results - Infection-Related Events

• Infections occurred across both age and frailty subgroups. See Tables: Infections Summary Across Age Subgroups (MAIA) and Infections Summary Across Frailty Subgroups (MAIA).²³

DARZALEX in Combination with Bortezomib, Melphalan, and Prednisone

ALCYONE (MMY3007; NCT02195479) is a phase 3, randomized, open-label, active-controlled, multicenter study evaluating the safety and efficacy of D-VMP compared with VMP alone for the treatment of NDMM in patients (N=706) who were ineligible for HDT with ASCT.²⁴

Final Efficacy and Safety Analysis of the ALCYONE Study

Mateos et al (2025)²⁵ reported the final efficacy and safety analysis results of the ALCYONE study at a median follow-up of 86.7 months. Results specific to infections are summarized below.

Safety Results - Infection-Related Events

• The incidence of grade 3/4 infections was higher in the D-VMP group compared with the VMP group (31% vs 15%). The most common infection-related TEAEs are summarized in Table: Most Common Infection-Related TEAEs (ALCYONE).²⁵

• The most common grade 3/4 infection in both treatment groups was pneumonia (D-VMP, 16%; VMP, 5%).²⁵
• Infection-related deaths are summarized in Table: Summary of Cause of Deaths Due to Infections (ALCYONE).³⁵

Treatment Discontinuation

• One patient in the VMP group discontinued treatment due to grade 5 infection (bacterial pneumonia), with no corresponding discontinuations in the D-VMP group.²⁵
  • Infection related treatment discontinuation is provided in Table: Treatment Discontinuation Due to Infection (ALCYONE).³⁵

Pooled Analysis of the MAIA and ALCYONE Studies

Bahlis et al (2026)²⁶ published a pooled analysis of the MAIA and ALCYONE studies to assess incidence, timing, and management of infection. A total of 710 patients in the D-Rd/D-VMP group and 719 patients in the Rd/VMP group were included in the pooled safety analysis. The median follow-up was 64.5 months (range, 0-77.6) for MAIA and 86.7 months (range, 0-97.9) for ALCYONE.

Results

• The most common treatment-emergent infections are summarized in Table: Most Common Treatment-Emergent Infections in Pooled MAIA/ALCYONE Safety Population.²⁶

• Respiratory infections were the most common type of infection across both groups.²⁶
  • Pneumonia was the most common grade 3/4 (18.2%) and grade 5 (0.7%) infection in the D-Rd/D-VMP group.
• Across treatment groups, any-grade infection led to treatment discontinuation in approximately 2% of patients.²⁶
• Within the first year of treatment, 481 patients (67.7%) in the D-Rd/D-VMP group vs 394 patients (54.8%) in the Rd/VMP group experienced onset of ≥1 treatment-emergent infection.²⁶
  • Onset of a grade 3/4 treatment-emergent infection in the first year occurred in 157 patients (22.1%) vs 112 patients (15.6%) in the D-VRd/D-VMP and Rd/VMP groups, respectively.
• The median treatment exposure in the D-Rd/D-VMP group (D-Rd, 47.5 months; D-VMP, 33.0 months) was longer than the Rd/VMP group (Rd, 22.6 months; VMP, 12.0 months).²⁶
  • The exposure adjusted incident rates (EAIRs) were slightly lower in the D-Rd/D-VMP group vs the Rd/VMP group (grade 3/4, 1.19 vs 1.41; grade 5, 0.07 vs 0.08, respectively).
• The median time to onset of any-grade infections was 4.9 months (95% CI, 4.1-5.6) in the D-Rd/D-VMP group and 7.2 months (95% CI, 5.7-9.0) in the Rd/VMP group.²⁶
• The highest incidence of grade 3/4 infections in both groups occurred within the first 6-month period of study treatment.²⁶
• More patients in the D-Rd/D-VMP group vs Rd/VMP group received infection prophylaxis (antibiotic, 27.0% vs 22.0%; antiviral, 73.4% vs 61.9%; antifungal, 5.2% vs 4.5%).²⁶

Phase 3 Study of DARZALEX FASPRO in Combination with Lenalidomide

AURIGA (MMY3021; NCT03901963) is a phase 3, randomized, open-label, active-controlled, multicenter study evaluating the conversion rate to MRD-negativity after maintenance treatment with D-R vs R alone in patients with NDMM who are anti-CD 38 naïve, have ≥VGPR, and are MRD-positive after ASCT.^27,28

Updated Efficacy and Safety Results of the AURIGA Study

Anderson et al (2025)²⁹ presented updated efficacy and safety results from the study at 24 months from the start of maintenance therapy, with a median follow-up of 40.3 months. Safety results related to infections have been summarized below.

Safety Results – Infection-Related Events

• Infection-related safety results are presented in Table: Infection-Related TEAEs (AURIGA).²⁹

Analysis of Clinically Relevant Subgroups of the AURIGA Study

Foster et al (2024)³⁰ presented a post hoc analysis of the phase 3 AURIGA study that evaluated clinically relevant subgroups at a median follow-up of 32.3 months. The clinically relevant subgroups included elderly and black patients, patients with high-risk disease per ISS disease staging, and patients with a high cytogenetic risk per standard, revised, and IMS 2024 high-risk criteria.

Safety Results - Infection-Related Events

• No unexpected safety concerns were observed in patients aged ≥65 years or in Black patients.³⁰
  • The median duration of therapy was 25 months (D-R, 30.5 months; R, 23.5 months) for patients aged <65 years and 24.4 months (D-R, 32.7 months; R, 19.2 months) for patients aged ≥65 years. Infection-related safety results based on age for patients with ≥1 TEAE are summarized in Table: Infection-Related Safety Results Based on Age for Patients With ≥1 TEAE (AURIGA).³⁰
  • The median duration of therapy was 23.7 months (D-R, 29.3 months; R, 18.9 months) for White patients and 25.4 months (D-R, 28.3 months; R, 25.4 months) for Black patients. Infection-related safety results based on race for patients with ≥1 TEAE are summarized in Table: Infection-Related Safety Results Based on Race for Patients With ≥1 TEAE (AURIGA).³⁰
• D-R maintenance did not increase grade 3/4 infection rates in patients ≥65 years of age.³⁰

Phase 3 Study of DARZALEX FASPRO in Combination with 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 TIE or for whom transplant is not planned as initial therapy (transplant deferred).³¹

Primary Analysis of the CEPHEUS Study

Usmani et al (2025)³¹ reported results from the phase 3 CEPHEUS study at a median follow-up of 58.7 months.

Safety Results - Infections

• The safety data were consistent with the established safety profile of each individual drug. Infection-related nonhematologic TEAEs in the safety population are summarized in Table: Infection-Related TEAEs in the Safety Population (CEPHEUS).³¹

• Overall, deaths were reported in 51 vs 60 patients from the D-VRd vs VRd arm, respectively.³¹
  • The COVID-19 pandemic impacted overall survival (OS) with 24 (21.6%) of all deaths in the study attributed to COVID-19 (D-VRd, n=15 vs VRd, n=9).
  • Overall, 21 COVID-19 deaths occurred during the peak of the pandemic in 2020 and 2021, with 3 additional deaths in 2022 (post-vaccine availability), and none in 2023 or 2024.
  • Regional variations were observed in pandemic impact. Brazil reported 54.2% of COVID-19 deaths (17.5% of the study population), while Poland had 16.7% of deaths (18.7% of the study population).
  • Two sensitivity analyses of OS adjusting for COVID-19 deaths showed a stronger treatment effect for D-VRd vs VRd (censoring COVID-19 deaths: hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.45-1.05] and considering COVID-19 deaths as a competing risk [HR for non-COVID mortality, 0.67; 95% CI, 0.44-1.03]).
• Grade 5 non-COVID-related TEAEs occurred in 10.7% vs 7.7% of patients from the D-VRd vs VRd arm, respectively.³¹
• Serious TEAEs occurred in 142 (72.1%) vs 131 (67.2%) of patients from the D-VRd vs VRd arm, respectively, with the most common serious TEAE being pneumonia (D-VRd, 13.7%; VRd, 12.8%). A summary of the serious TEAEs is presented in Table: Infection-Related Serious TEAEs (≥2%) in the Safety Population (CEPHUS).³¹

Age and Frailty Analysis of the CEPHEUS Study

Venner et al (2026)²³ presented the results of an age and frailty analysis of TIE patients in the MAIA and CEPHEUS studies. Results specific to infections in the CEPHEUS study are summarized below.

Safety Results - Infection-Related Events

• Infections occurred across both age and frailty subgroups. See Tables: Infections Summary Across Age Subgroups (CEPHEUS) and Infections Summary Across Frailty Subgroups (CEPHEUS).²³

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 03 June 2026. 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.