TECVAYLI®

(teclistamab-cqyv)

Medical inquiries

Connect with my medical science liaison

Chat live

Available Monday - Friday 9AM - 4:30PM ET

Call me now

Available Monday - Friday 9AM - 7:30PM ET

Email your inquiry

Call 1-800-526-7736

Available Monday - Friday 9AM - 8PM ET

Live video

Available Monday - Friday 9AM - 4:30PM ET

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.

TECVAYLI® (teclistamab-cqyv)

Medical Information

+ Save link

DARZALEX + DARZALEX FASPRO - Adverse Event - Incidence of Infections in Patients with Relapsed/Refractory Multiple Myeloma

Last Updated: 06/27/2025

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.
LYRA: phase 2 study evaluating the safety and efficacy of DARZALEX in combination with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) for the treatment of MM in patients who have not received previous treatment or have relapsed after receiving only 1 line of treatment. Results from both cohorts of patients have been summarized. The most common infection-related TEAE (any grade) was URTI (50%) in the relapsed multiple myeloma (RMM) arm.¹⁶^,¹⁷
- DARZALEX/DARZALEX FASPRO is not approved by the regulatory agencies for use in combination with CyBorD for the treatment of MM. Janssen does not recommend the use of DARZALEX/DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
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.¹⁸
- All-grade infection-related TEAE was URTI in part 1 (1200 mg group, 38%; 1800 mg group, 24%) and part 2 (DARZALEX FASPRO, 8%).¹⁸
- In the updated results from part 2, the most common all-grade infection-related TEAEs was nasopharyngitis (24%).¹⁹
- 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%).²⁰
TRIMM-2 is an ongoing, phase 1b, multicohort study evaluating DARZALEX FASPRO regimens in combination with bispecific T-cell redirection antibodies in patients with RRMM.²¹
- Rodriguez-Otero et al (2022)²² presented the updated results from the TECVAYLI™ SC + DARZALEX FASPRO cohort of the TRIMM-2 study. Infections were reported in 44 (67.7%) patients, of which 27.7% were grade 3/4.
  - DARZALEX FASPRO is not approved by regulatory agencies for use in combination with TECVAYLI for the treatment of MM. Janssen does not recommend the use of DARZALEX/DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
- D’Souza et al (2024)²³ presented preliminary safety and efficacy results of 10 patients with RRMM who had received ≥3 prior lines of therapy (LOT) from the TALVEY SC + DARZALEX FASPRO + pomalidomide cohort of the TRIMM-2 study. Any grade infections were reported in 90.0% of patients. Most common (occurring in ≥15% of patients) any grade infections were upper respiratory tract infection (40.0%), pneumonia (40.0%), sinusitis (40.0%), COVID-19 (40.0%) and COVID-19 pneumonia (10.0%).
- Bahlis et al (2024)²⁴ presented first results from TALVEY SC + DARZALEX FASPRO + pomalidomide cohort of the TRIMM-2 study. In the TALVEY 0.4 mg/kg SC weekly (QW) + DARZALEX FASPRO + pomalidomide group, any grade infections were reported in 72.2% of patients; most common (occurring in ≥10% of patients) any grade infections were COVID-19 (38.9%), upper respiratory tract infection (11.1%), viral upper respiratory tract infection (16.7%) and sinusitis (22.2%). In the TALVEY 0.8 mg/kg SC every other week (Q2W) + DARZALEX FASPRO + pomalidomide group, any grade infections were reported in 78.0% of patients; most common (occurring in ≥10% of patients) any grade infections were COVID-19 (27.1%), upper respiratory tract infection (25.4%), pneumonia (16.9%) and viral upper respiratory tract infection (10.2%).
- Dholaria et al (2023)²⁵ presented the updated results from the TALVEY™ SC + DARZALEX FASPRO cohort of the TRIMM-2 study. The most common any grade infection-related adverse event in the TALVEY 0.4 mg/kg SC weekly (QW) + DARZALEX FASPRO vs TALVEY 0.8 mg/kg SC (Q2W) + DARZALEX FASPRO cohorts was coronavirus disease 2019 ([COVID-19], 28.6% vs 23.5%).
  - DARZALEX FASPRO is not approved by regulatory agencies for use in combination with TALVEY for the treatment of MM. Janssen does not recommend the use of DARZALEX/DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
MajesTEC-2 (MMY1004) is an ongoing, phase 1b, multicohort study evaluating TECVAYLI in combination with other anticancer therapies in patients with MM.²⁶^,²⁷ The most common any grade infection-related TEAE was COVID-19 (37.5%).²⁶
- D’Souza et al (2024)²³ presented preliminary safety and efficacy results of patients with MM and 1-3 prior lines of treatments (n=17) from the TALVEY SC + DARZALEX FASPRO + pomalidomide cohort of the MajesTEC-2 study. Any grade infections were reported in 94.1% of patients. Most common (occurring in ≥15% of patients) any grade infections were upper respiratory tract infection (47.1%), pneumonia (23.5%), sinusitis (23.5%), COVID-19 (17.6%) and COVID-19 pneumonia (23.5%).
  - DARZALEX FASPRO is not approved by regulatory agencies for use in combination with lenalidomide and TECVAYLI for the treatment of MM. Janssen does not recommend the use of DARZALEX/DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
CARTITUDE-4 (MMY3002) is a phase 3, randomized, open-label study evaluating the efficacy and safety of ciltacabtagene autoleucel (cilta-cel) vs standard care (physician's choice of pomalidomide, bortezomib, and dexamethasone [PVd] or D-Pd) in adult patients with lenalidomide-refractory MM after 1-3 prior line(s) of therapy. The most common all-grade infection-related adverse event (AE) was URTI (cilta-cel, 18.8%; standard care, 26.0%).²⁸

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.
TECVAYLI (teclistamab-cqyv) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf.
TALVEY (talquetamab-tgvs) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-pi.pdf.
CARVYKTI (ciltacabtagene autoleucel) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-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).

Any Grade or Grade 3/4 Infection-Related TEAEs (CASTOR)²

Event, n (%)	D-Vd (n=243)		Vd (n=237)
Event, n (%)	Any Grade	Grade 3/4	Any Grade	Grade 3/4
URTI	90 (37.0)	6 (2.5)	43 (18.1)	1 (0.4)
Pneumonia	40 (16.5)	26 (10.7)	32 (13.5)	24 (10.1)
Bronchitis	38 (15.6)	7 (2.9)	15 (6.3)	3 (1.3)
Abbreviations: D-Vd, DARZALEX + bortezomib + dexamethasone; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection; Vd, bortezomib + dexamethasone.

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.

Most Common Any Grade (≥20%) and Grade ≥3 (≥5%) Infection-Related TEAEs and TEAEs of Interest (CANDOR)⁴

Event, n (%)	D-Kd (n=308)		Kd (n=153)
Event, n (%)	Any Grade	Grade ≥3	Any Grade	Grade ≥3
Most Common TEAEs
URTI	105 (34.1)	12 (3.9)	37 (24.2)	2 (1.3)
Pneumonia	79 (25.6)	57 (18.5)	24 (15.7)	14 (9.2)
TEAEs of interest
Respiratory tract infection	243 (78.9)	117 (38.0)	90 (58.8)	27 (17.6)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.

Infection-Related Fatal TEAEs²⁹

TEAE, n (%)	D-Kd (n=308)	Kd (n=153)
COVID-19 pneumonia	5 (1.6)	1 (0.7)
Pneumonia	5 (1.6)	0 (0.0)
Sepsis	3 (1.0)	2 (1.3)
Acinetobacter infection	1 (0.3)	0 (0.0)
COVID-19	1 (0.3)	0 (0.0)
Respiratory tract infection	1 (0.3)	0 (0.0)
Influenza	0 (0.0)	1 (0.7)
Abbreviations: COVID-19, coronavirus disease 2019; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event.

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%).

Any Grade or Grade 3/4 Infection-Related TEAEs (POLLUX)⁶

TEAE, n (%)	D-Rd (n=283)		Rd (n=281)
TEAE, n (%)	Any Grade	Grade 3/4	Any Grade	Grade 3/4
URTI	125 (44.2)	6 (2.1)	79 (28.1)	5 (1.8)
Nasopharyngitis	100 (35.3)	0	62 (22.1)	0
Pneumonia	80 (28.3)	49 (17.3)	49 (17.4)	31 (11.0)
Bronchitis	63 (22.3)	9 (3.2)	50 (17.8)	9 (3.2)
Influenza	46 (16.3)	11 (3.9)	24 (8.5)	3 (1.1)
Febrile neutropenia	18 (6.4)	18 (6.4)	8 (2.8)	8 (2.8)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.

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%).

Most Common Any Grade (≥15%) and Grade 3/4 (≥5%) Infection-Related TEAEs in the Safety Population (APOLLO)¹⁴

TEAE, n (%)	Any Grade		Grade 3/4
TEAE, n (%)	D-Pd (n=149)	Pd (n=150)	D-Pd (n=149)	Pd (n=150)
URTI	37 (24.8)	24 (16.0)	0	3 (2.0)
Pneumonia	30 (20.1)	21 (14.0)	21 (14.1)	11 (7.3)
LRTI	29 (19.5)	24 (16.0)	17 (11.4)	14 (9.3)
COVID-19	18 (12.1)	3 (2.0)	8 (5.4)	1 (0.7)
Febrile neutropenia	13 (8.7)	5 (3.3)	13 (8.7)	5 (3.3)
Abbreviations: COVID-19, Coronavirus Disease 2019; D-Pd, DARZALEX FASPRO + pomalidomide + dexamethasone; LRTI, lower respiratory tract infection; Pd, pomalidomide + dexamethasone; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.

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

Most Common Infection-Related Any Grade (≥25%) and Grade 3/4 (≥5%) TEAEs in the D-Kd arm (PLEIADES)⁹

Event, n%	D-Kd (n=66)
Event, n%	Any Grade	Grade 3/4
Nasopharyngitis	17 (25.8)	0
URTI	12 (18.2)	0
Abbreviation: D-Kd, DARZALEX FASPRO + carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.

DARZALEX in Combination with CyBorD in RMM

LYRA (MMY2012; NCT02951819) is a phase 2, single-arm, open-label, multicenter study evaluating the safety and efficacy of DARZALEX when administered in combination with CyBorD for the treatment of MM in patients who have not received previous treatment or have relapsed after receiving only 1 line of treatment.¹⁶^,³⁰ Yimer et al (2022)¹⁶ reported the end-of-study results of the LYRA study, with a median follow-up of 35.3 months for the RMM arm. Safety results related to infections have been summarized below.

Safety Results - Infection-Related - End-of-Study Analysis

In the RMM arm, the most common any grade infection-related TEAE was URTI (50.0%) and the most common serious TEAE was pneumonia (14.3%).¹⁷
Infection-related TEAEs are summarized in Tables: Most Common Any Grade (≥25%) and Grade 3/4 (≥10%) Infection-Related TEAEs in the Safety Analysis Set (LYRA) and Most Common Any Grade (≥20%) and Grade 3/4 (≥5%) Infection-Related TEAEs Occurring During the Maintenance Phase in the Safety Analysis Set (LYRA).

Most Common Any Grade (≥25%) and Grade 3/4 (≥10%) Infection-Related TEAEs in the Safety Analysis Set (LYRA)^a,¹⁷

Patients With ≥1 TEAE, n (%)	RMM (n=14)
Patients With ≥1 TEAE, n (%)	Any Grade	Grade 3/4
URTI	7 (50.0)	0
Nasopharyngitis	5 (35.7)	0
Pneumonia	4 (28.6)	2 (14.3)
Sinusitis	4 (28.6)	0
Abbreviations: RMM, relapsed multiple myeloma; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection. ^aThe safety analysis set includes all patients who received ≥1 dose of study treatment.

Most Common Any Grade (≥20%) and Grade 3/4 (≥5%) Infection-Related TEAEs Occurring During the Maintenance Phase in the Safety Analysis Set (LYRA)^a,¹⁷

Patients With ≥1 TEAE, n (%)	RMM (n=10)
Patients With ≥1 TEAE, n (%)	Any Grade	Grade 3/4
Pneumonia	4 (40.0)	2 (20.0)
Upper respiratory tract infection	3 (30.0)	0
Nasopharyngitis	2 (20.0)	0
Abbreviations: RMM, relapsed multiple myeloma; TEAE, treatment-emergent adverse event. ^aThe safety analysis set includes all patients who received ≥1 dose of study treatment.

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.

Most Common Any Grade (≥10%) and Grade 3/4 (≥5%) Infection-Related TEAEs in the Safety-Evaluable Population (COLUMBA)^a,¹²

TEAEs, n (%)	DARZALEX (n=258)		DARZALEX FASPRO (n=260)
TEAEs, n (%)	Any grade	Grade 3/4	Any grade	Grade 3/4
URTI	30 (11.6)	2 (0.8)	44 (16.9)	0
Nasopharyngitis	21 (8.1)	0	28 (10.8)	1 (0.4)
Pneumonia	19 (7.4)	13 (5)	16 (6.2)	13 (5)
Abbreviations: IRR, infusion-related reaction; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.^aThe safety-evaluable population includes all patients who underwent randomization and received ≥1 dose of study treatment.

Most Common Grade 3/4 (≥5%) Infection-Related TEAEs Across Body Weight Subgroups (COLUMBA)¹²

TEAEs, n (%)	DARZALEX				DARZALEX FASPRO
TEAEs, n (%)	≤65 kg (n=92)	>65-85 kg (n=105)	>85 kg (n=61)		≤65 kg (n=93)	>65-85 kg (n=102)	>85 kg (n=65)
URTI	0	2 (1.9)		0	0	0	0
Nasopharyngitis	0	0		0	0	0	1 (1.5)
Pneumonia	7 (7.6)	3 (2.9)		3 (4.9)	5 (5.4)	1 (1.0)	7 (10.8)
Abbreviations: TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.

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

Most Common Infection-Related Any Grade (≥25%) and Grade 3/4 (≥5%) TEAEs in the D-Kd arm (EQUULEUS)⁹

Event, n (%)	D-Kd (N=85)
Event, n (%)	Any grade	Grade 3/4
URTI	38 (44.7)	3 (3.5)
Nasopharyngitis	15 (17.6)	0
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.

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.

Most Common (≥25%) Infection-Related TEAEs in Part 2 of GEN503 Study¹⁰

Event, n (%)	D-Rd (N=32)
Event, n (%)	All Grades	Grade 3/4
Nasopharyngitis	10 (31.3)	0 (0)
Bronchitis	9 (28.1)	1 (3.1)
URTI	9 (28.1)	1 (3.1)
Rhinitis	8 (25)	0 (0)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.

CLINICAL DATA – RELAPSED/REFRACTORY – IN COMBINATION WITH BISPECIFIC ANTIBODY

DARZALEX FASPRO in Combination with TECVAYLI (TRIMM-2 Study)

TRIMM-2 (MMY1002; NCT04108195) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating DARZALEX FASPRO in combination with bispecific T-cell redirection antibodies (TECVAYLI and TALVEY) in patients with RRMM who had received ≥3 prior LOT.²¹ Rodriguez-Otero et al (2022)²² presented the updated results from the TECVAYLI SC + DARZALEX FASPRO cohort of the TRIMM-2 study at a median follow-up of 8.6 months. Safety results related to infections have been summarized below.

Safety Results - Infection-Related

Infections were reported in 44 (67.7%) patients, of which 27.7% were grade 3/4.
Four deaths were reported due to adverse events (AEs). None were related to TECVAYLI or DARZALEX FASPRO (bacterial pneumonia, sepsis, hepatic failure, COVID-19).

DARZALEX FASPRO in Combination with TALVEY (TRIMM-2 Study)

Dholaria et al (2023)²⁵ presented the updated efficacy and safety results of the TALVEY SC QW + DARZALEX FASPRO cohort at a median follow-up of 16.8 months and TALVEY SC (Q2W) + DARZALEX FASPRO cohort at median follow-up of 15.0 months. Safety results related to infections have been summarized below.

Safety Results - Infection-Related

Infections were generally low grade, except for pneumonia, most cases of which were of grade 3/4. The incidence and types of infections are presented in Table: Any Grade or Grade 3/4 Infection-Related AEs (TRIMM-2; TALVEY + DARZALEX FASPRO).
Among patients with grade ≥3 infections, 75.0% had onset within the first 6 months.
Overall, 95.4% of patients received antibacterial, antifungal, or antiviral prophylaxis.
Overall, 10.8% of patients had opportunistic infections, and 3.1% had cytomegalovirus reactivation.
Pneumonia (treatment-related) caused the death of 1 patient who received TALVEY 0.8 mg/kg SC Q2W + DARZALEX FASPRO.
In both the cohorts combined, no reduction in the total CD19 B cells was observed, which may explain the relatively low grade 3/4 infection rate.
Immunoglobulin G (IgG) <500 mg/dL was reported in 35.4% of patients at baseline, which increased to 86.2% post-baseline; 33.8% of these patients received intravenous immunoglobulin.

Any Grade or Grade 3/4 Infection-Related AEs (TRIMM-2; TALVEY + DARZALEX FASPRO cohort)²⁵

Events, n (%)	TALVEY 0.4 mg/kg SC QW + DARZALEX FASPRO (n=14)		TALVEY 0.8 mg/kg SC Q2W + DARZALEX FASPRO (n=51)
Events, n (%)	Any Grade	Grade 3/4	Any Grade	Grade 3/4
Infections (≥5%)	8 (57.1)	3 (21.4)	37 (72.5)	13 (25.5)
COVID-19	4 (28.6)	0 (0)	12 (23.5)	2 (3.9)
Urinary tract infection	0 (0)	0 (0)	10 (19.6)	2 (3.9)
Pneumonia	2 (14.3)	1 (7.1)	7 (13.7)	7 (13.7)
Upper respiratory tract infection	3 (21.4)	0 (0)	4 (7.8)	0 (0)
Other respiratory tract infections	1 (7.1)	0 (0)	7 (13.7)	1 (2.0)
Abbreviations: AE, adverse event; COVID-19, Coronavirus Disease 2019; Q2W, every other week; QW, weekly.Note: Data cut-off was April 6, 2023

DARZALEX FASPRO in Combination with TECVAYLI and Lenalidomide (MajesTEC-2 Study; Cohort E)

MajesTEC-2 (MMY1004; NCT04722146) is an ongoing, phase 1b, multicohort study evaluating the safety and efficacy of TECVAYLI in combination with other anticancer treatments in patients with MM.²⁶^,²⁷ Searle et al (2022)²⁶ presented initial results from cohort E that evaluated the safety and efficacy of TECVAYLI + DARZALEX FASPRO + lenalidomide in 32 patients with MM and 1-3 prior lines of treatments, including a PI and an immunomodulatory drug. Safety results related to infections have been summarized below.

Safety Results - Infection-Related

The incidence of ≥1 infections (any grade) was reported in 90.6% of patients (n=29). The incidence of ≥1 grade 3/4 infections was reported in 37.5% of patients (n=12).
The most common infections (any grade; ≥25%) were: COVID-19 (37.5%), upper respiratory infections (31.3%), and pneumonia (25.0%).
- Among the 12 patients that reported COVID-19 during treatment; 4 patients (33.3%) were not vaccinated.
The incidence and types of infections are presented in Table: MajesTEC-2 (Cohort E): Infections (Any Grade; ≥25% and/or Grade 3/4; ≥3.1%).
- Additionally, grade 3/4 AEs for anorectal infection (n=1), gastroenteritis (n=1), haemophilius infection (n=1), urinary tract infection (n=1) have been reported.

Any Grade (≥25%) and/or Grade 3/4 (≥3.1%) Infection AEs (MajesTEC-2 [Cohort E])²⁶

Event, n (%)	N=32
Event, n (%)	Any Grade	Grade 3/4
Patients with ≥1 infection	29 (90.6)	12 (37.5)
COVID-19^a	12 (37.5)	4 (12.5)
Upper respiratory infection	10 (31.3)	0
Pneumonia	8 (25.0)	5 (15.6)
COVID-19 pneumonia	4 (12.5)	1 (3.1)
Sepsis	3 (9.4)	3 (9.4)
Pneumonia pseudomonal	2 (6.3)	2 (6.3)
Cytomegalovirus infection^b	2 (6.3)	2 (6.3)
Abbreviations: AE, adverse event; COVID-19, Coronavirus disease 2019.^aIncludes COVID-19 pneumonia.^bIncludes cytomegalovirus infection reactivation, cytomegalovirus syndrome.

Cilta-cel vs Standard Care (Physician's Choice of PVd or D-Pd) - CARTITUDE-4 Study

CARTITUDE-4 (MMY3002; clinicaltrials.gov identifier: NCT04181827) is an ongoing, phase 3, randomized, open-label study evaluating the efficacy and safety of cilta-cel vs standard care (physician's choice of PVd or D-Pd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOT.²⁸ San-Miguel et al 2023²⁸ reported efficacy and safety results from the interim analysis of this study. Safety results related to infections have been summarized below.

Safety Results - Infection-Related

Infections occurred in 62.0% of cilta-cel patients (n=129) and in 71.2% of standard care arm patients (n=148).
- COVID-19 (includes preferred terms COVID-19, COVID-19 pneumonia, and asymptomatic COVID-19) infection was reported in 13.9% of cilta-cel patients (n=29) and in 26.4% of standard care patients (n=55). Grade 3/4 COVID-19 occurred in 2.9% of cilta-cel patients (n=6) and in 5.8% of standard care patients (n=12).
The incidence and types of infections are presented in Table: All Grade and Grade 3/4 Infection-Related AEs (CARTITUDE-4).

All Grade and Grade 3/4 Infection-Related AEs (CARTITUDE-4)²⁸

Event^a, n (%)	Cilta-cel (n=208)		Standard Care (n=208)
Event^a, n (%)	All Grade	Grade 3/4	All Grade	Grade 3/4
Infections	129 (62.0)	56 (26.9)	148 (71.2)	51 (24.5)
Upper respiratory tract infections^b	39 (18.8)	4 (1.9)	54 (26.0)	4 (1.9)
COVID-19^c	29 (13.9)	6 (2.9)	55 (26.4)	12 (5.8)
Lower respiratory tract/lung infections^d	19 (9.1)	9 (4.3)	36 (17.3)	8 (3.8)
Abbreviations: AE, adverse event; Cilta-cel, ciltacabtagene autoleucel; COVID-19, coronavirus disease 2019. ^aAEs were graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.^bIncludes preferred terms upper respiratory tract infection, nasopharyngitis, sinusitis, rhinitis, tonsillitis, pharyngitis, laryngitis, and pharyngotonsillitis. ^cIncludes preferred terms COVID-19, COVID-19 pneumonia, and asymptomatic COVID-19. In addition, there were 7 (cilta-cel) and 1 (standard-of-care) grade 5 events. ^dIncludes preferred terms lower respiratory tract infection, pneumonia, and bronchitis.

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.

References

Show

1	Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754-766.
2	Sonneveld P, Khan AC, Weisel K, et al. Overall survival with daratumumab, bortezomib, and dexamethasone in previously treated multiple myeloma (CASTOR): a randomized, open-label, phase III trial. J Clin Oncol. 2023;41:1600-1609.
3	Dimopoulos M, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396(10245):186-197.
4	Usmani SZ, Quach H, Mateos MV, et al. Final analysis of carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone in the CANDOR Study. Blood Adv. 2023;7(14):3739-3748.
5	Dimopoulos M, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319-1331.
6	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.
7	Usmani S, Nahi H, Plesner T, et al. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trials. Lancet Haematol. 2020;7:e447-e455.
8	Chari A, Suvannasankha A, Fay J, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017;130:974-981.
9	Moreau P, Chari A, Oriol A, et al. Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS. Blood Cancer J. 2023;13(1):33.
10	Plesner T, Arkenau H, Gay F, et al. Enduring efficacy and tolerability of daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (GEN503): final results of an open-label, phase 1/2 study. Br J Haematol. 2019;183:e35-e39.
11	Mateos M, Nahi H, Legiec W, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020;7:e370-e380.
12	Usmani S, Nahi H, Legiec W, et al. Final analysis of the phase 3 non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. Haematologica. 2022;107:2408-2417.
13	Dimopoulos M, Terpos E, Boccadoro M, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:801-812.
14	Dimopoulos M, Terpos E, Boccadoro M, et al. Subcutaneous daratumumab plus pomalidomide and dexamethasone (D-Pd) versus pomalidomide and dexamethasone (Pd) alone in patients with relapsed or refractory multiple myeloma (RRMM): overall survival results from the phase 3 APOLLO study. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA.
15	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.
16	Yimer H, Melear J, Faber E, et al. Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for multiple myeloma: final results of the LYRA study. Leuk Lymphoma. 2022;63(10):2383-2392.
17	Yimer H, Melear J, Faber E, et al. LYRA: A phase 2 study of daratumumab (dara) plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in newly diagnosed and relapsed patients (Pts) with multiple myeloma (MM). Oral Presentation presented at: 60th American Society of Hematology (ASH) Annual Meeting & Exposition; December 1-4; San Diego, CA.
18	Chari A, Nahi H, Mateos M, et al. Subcutaneous delivery of daratumumab in patients with relapsed or refractory multiple myeloma (RRMM): PAVO, an open-label, multicenter, dose escalation phase 1b study. Oral Presentation presented at: The Annual Meeting of the American Society of Hematology (ASH); December 9-12, 2017; Atlanta, GA.
19	San-Miguel J, Usmani S, Mateos M, et al. Subcutaneous daratumumab in patients with relapsed or refractory multiple myeloma: Part 2 of the open-label, multicenter, dose-escalation phase 1b study (PAVO). Haematologica. 2021;106:1725-1732.
20	Nahi H, Usmani S, Mateos M, et al. Corticosteroid tapering is a safe approach in patients with relapsed or refractory multiple myeloma receiving subcutaneous daratumumab: part 3 of the open-label, multicenter, phase 1b PAVO study. Leuk Lymphoma. 2023;64(2):468-472.
21	Janssen Research & Development, LLC. A phase 1b study of subcutaneous daratumumab regimens in combination with bispecific T cell redirection antibodies for the treatment of subjects with multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 June 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT04108195 NLM Identifier: NCT04108195.
22	Rodriguez-Otero P, D’Souza A, Reece D, et al. A Novel, immunotherapy-based approach for the treatment of relapsed/refractory multiple myeloma: updated phase 1b results for daratumumab in combination with teclistamab (a BCMA X CD3 bispecific antibody). Poster presented at: 2022 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL/Virtual Meeting.
23	D’Souza A, Costa LJ, San-Miguel J, et al. Teclistamab, daratumumab, and pomalidomide in patients with relapsed/refractory multiple myeloma: results from the MajesTEC-2 cohort A and TRIMM-2 studies. Oral Presentation presented at: The 66th American Society of Hematology (ASH) Annual Meeting; December 7-10, 2024; San Diego, CA.
24	Bahlis N, van de Donk NWCJ, Reece D, et al. Talquetamab + daratumumab + pomalidomide in patients with relapsed/refractory multiple myeloma: results from the phase 1b TRIMM2 study. Oral Presentation presented at: 21st International Myeloma Society (IMS) Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil.
25	Dholaria B, Weisel K, Mateos M, et al. Talquetamab + daratumumab in patients with relapsed/refractory multiple myeloma: updated TRIMM-2 results. Oral presentation presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 2-6, 2023; Chicago, IL.
26	Searle E, Quach H, Wong S, et al. Teclistamab in combination with subcutaneous daratumumab and lenalidomide in patients with multiple myeloma: Results from one cohort of MajesTEC-2, a phase 1b, multicohort study. Oral presentation presented at: 64th American Society of Hematology (ASH) Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA.
27	Janssen Research & Development, LLC. A Multi-arm phase 1b study of teclistamab with other anticancer therapies in participants with multiple myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 June 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT04722146 NLM Identifier NCT04722146. 2024.
28	San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347.
29	Usmani S, Quach H, Mateos M, et al. Supplement to: Final analysis of carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone in the CANDOR Study. Blood Adv. 2023;7(14):3739-3748.
30	Yimer H, Melear J, Faber E, et al. Daratumumab, bortezomib, cyclophosphamide and dexamethasone in newly diagnosed and relapsed multiple myeloma: LYRA study. Br J Haematol. 2019;185:492-502.

Endchat

Chat live