SUMMARY

• Janssen does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
• Hematologic adverse events (AEs) have been reported in the MonumenTAL-1, MonumenTAL-2, TRIMM-2, and RedirecTT-1 studies.^1-7
• MonumenTAL-1 (MMY1001) is an ongoing, open-label, phase 1/2 study evaluating the efficacy and safety of TALVEY in patients with relapsed or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.^1,4,8
  • Schinke et al (2024)⁹ presented the incidence of hematologic AEs from a subgroup analysis in Black and White patients at a median follow-up of 26 months for the Black subgroup and 31 months for the White subgroup. The subgroup of patients received TALVEY at the recommended phase 2 doses (RP2Ds) of 0.4 mg/kg subcutaneous (SC) weekly (QW) and 0.8 mg/kg SC every other week (Q2W).
  • Schinke et al (2023)¹ presented the incidence of hematologic AEs from the phase 2 portion of MonumenTAL-1 study at a median follow-up of 18.8 months for the 0.4 mg/kg SC QW cohort, 12.7 months for the 0.8 mg/kg SC Q2W cohort, and 14.8 months for the prior T-cell redirection therapy (TCR)-exposed cohort.
  • Jakubowiak et al (2023)¹⁰ presented the incidence of hematologic AEs in patients with prior TCR, including an additional 19 patients enrolled in the MonumenTAL-1 study since the prior analysis, at a median follow-up of 18.4 months for the overall prior TCR cohort, 18.4 months for the prior chimeric antigen receptor-modified T-cells (CAR-T) cohort, and 16.3 months for the prior bispecific antibody (BsAb) cohort.
  • Chari et al (2022)^4,5 published the incidence of hematologic AEs from the phase 1 portion of the MonumenTAL-1 study. Patients received TALVEY at the first RP2D of 0.405 mg/kg SC QW (median follow-up, 11.7 months), or at the second RP2D of 0.8 mg/kg SC Q2W (median follow-up, 4.2 months).
  • Per protocol, dose delays were the primary method for managing hematologic AEs in the MonumenTAL-1 Study. Please see below for a summary of permitted medications, mitigation strategies and dose modification guidance for the management of hematologic AEs.⁸
• MonumenTAL-2 (MMY1004) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with multiple myeloma (MM).^6,11-13
  • Cohort D is evaluating the efficacy and safety of TALVEY + DARZALEX FASPRO^® (daratumumab hyaluronidase) and lenalidomide in 34 patients with newly diagnosed multiple myeloma (NDMM).¹²
    • Nooka et al (2024)¹² presented the incidence of hematologic AEs of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months (range, 10.0-14.6) and the TALVEY 0.8 mg/kg every 4 weeks (Q4W) + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0).
  • Cohort E is evaluating the safety and efficacy of TALVEY + pomalidomide in 35 patients with RRMM.¹³
    • Searle et al (2024)¹³ presented the incidence of hematologic AEs in the TALVEY + pomalidomide cohort from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1).
• RedirecTT-1 (MMY1003) is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of the TALVEY and TECVAYLI^® (teclistamab-cqyv) combination in patients with RRMM.^3,7,14,15
  • Cohen et al (2025)⁷ published the incidence of hematologic AEs from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months (range, 0.5-37.1) in the all dose levels (dose levels 1-5) cohort.
• TRIMM-2 (MMY1002) is an ongoing, phase 1b, multicohort open-label study evaluating the efficacy and safety of DARZALEX FASPRO + TECVAYLI or TALVEY with or without pomalidomide in patients with RRMM.^2,16,17
  • Bahlis et al (2024)¹⁷ presented the incidence of hematologic AEs in the TALVEY  0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 15.8 months (range, 3.2-37.9) and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 17.5 months (range, 0.2-37.7).
  • Dholaria et al (2023)² presented the incidence of hematologic AEs from the TALVEY + DARZALEX FASPRO cohorts at a median follow-up of 16.8 months for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO cohort and 15.0 months for the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO cohort.

PRODUCT LABELING

• TALVEY (talquetamab-tgvs) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-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.

CLINICAL DATA - Monumental-1 Study

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^18,19

The study was conducted in 3 parts; the primary objectives are listed below¹:

• Part 1 (phase 1; dose escalation): to characterize the safety of TALVEY and determine the RP2Ds and schedule.
• Part 2 (phase 1; dose expansion): to further characterize the safety of TALVEY at the RP2Ds.
• Part 3 (phase 2): to evaluate the efficacy of TALVEY at the RP2Ds.

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 3 cohorts^1,10:

• TCR naïve: 0.4 mg/kg SC QW, not previously exposed to TCR such as CAR-T or BsAb (prior B-cell maturation antigen [BCMA] antibody-drug conjugate [ADC] allowed).
• TCR naïve: 0.8 mg/kg SC Q2W, not previously exposed to TCRs (prior BCMA ADC allowed).
• Prior TCR: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W, have been previously exposed to TCRs.
  • Among the prior TCR-exposed cohort, patients were divided based on type of TCR (CAR-T, BsAb or CAR-T and BsAb).
• Key eligibility criteria (Part 3; Phase 2):
  • Measurable MM.¹⁰
  • ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.¹⁰
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.¹⁰
• Key exclusion criteria (Part 3; Phase 2):
  • Prior grade 3 or higher cytokine release syndrome (CRS; per Lee criteria 2014²⁰) related to any TCR or any prior G protein-coupled receptor class C group 5 member D (GPRC5D)-targeting therapy.⁸
  • Received cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within 14 days prior to study drug (not including premedication).⁸
• Primary endpoint: overall response rate (ORR).¹
• Key secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival, safety, immunogenicity, and pharmacodynamics.¹

Schinke et al (2024)⁹ presented the incidence of hematologic AEs from a subgroup analysis in Black patients who received TALVEY at the RP2Ds of 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W in phase 1/2 of the MonumenTAL-1 study at a median follow-up of 26 months for the Black subgroup and 31 months for the White subgroup.

Safety Results

• Details on hematologic AEs are summarized in Table: MonumenTAL-1 Study: Summary of Hematologic AEs in Black vs White Patients (≥30% in Either Group).

Schinke et al (2023)¹ presented the incidence of hematologic AEs from the MonumenTAL-1 study at a median follow-up of 18.8 months for the 0.4 mg/kg SC QW cohort, 12.7 months for the 0.8 mg/kg SC Q2W cohort, and 14.8 months for the prior TCR-exposed cohort.

Safety Results

• The incidence of any grade and grade 3/4 hematologic AEs reported in patients in the 0.4 mg/kg SC QW, 0.8 mg/kg SC Q2W, and prior TCR cohorts is presented in Table: MonumenTAL-1 (Phase 2) Study: Hematologic AEs.

Jakubowiak et al (2023)¹⁰ presented the incidence of hematologic AEs in patients with prior TCR, including an additional 19 patients enrolled in the MonumenTAL-1 study since the prior analysis, at a median follow-up of 18.4 months for the overall prior TCR cohort and the prior CAR-T cohort and 16.3 months for the prior BsAb cohort.

Safety Results

• A summary of select hematologic AEs in patients with prior TCR is presented in Table: MonumenTAL-1 Study: Select Hematologic AEs (Prior TCR).
  • Patients with prior exposure to CAR-T had similar rates of cytopenias compared with patients with prior exposure to BsAb.

Chari et al (2022)⁴ published the incidence of hematologic AEs from the phase 1 portion of the MonumenTAL-1 study at a median follow-up of 11.7 months (range, 1.0-21.2) for the 0.405 mg/kg SC QW cohort and 4.2 months (range, 0.7-13.7) for the 0.8 mg/kg SC Q2W cohort.

Study Design/Methods

• Patients received TALVEY at a dose of 0.0005-0.18 mg/kg intravenously (IV) QW or Q2W, at the first RP2D of 0.405 mg/kg SC QW, or at the second RP2D of 0.8 mg/kg SC Q2W.
• Additional IV and SC doses were evaluated in order to determine the RP2Ds.

Safety Results

• The incidence of any grade and grade 3/4 hematologic AEs reported in patients in the 0.405 mg/kg SC QW and 0.8 mg/kg SC Q2W cohorts are summarized in Table: MonumenTAL-1 (Phase 1) Study: Hematologic AEs.
• Hematologic AEs were the most commonly reported grade 3 or 4 AEs. Cytopenias were reversible and mostly limited to patients who had received step-up doses and early full doses through cycle 2.

MonumenTAL-1 Protocol (phase 2, Part 3) - Description and Management of Hematologic AEs⁸

Key Permitted Medications Related to Hematologic AEs

• Patients are to receive full supportive care during the study. The following are examples of supportive therapies related to hematologic events that may be used during the study:
  • Growth factor support, erythropoietin-stimulating agents, platelet-stimulating factor, and transfusions are permitted to treat symptoms or signs of neutropenia, anemia, or thrombocytopenia according to local standards of care.

Potential Risks Associated with TALVEY and Mitigation Strategies for Cytopenias

• Mitigation strategies for risk of cytopenias included frequent monitoring of hematological parameters and supportive care (eg, blood and thrombocyte transfusions, granulocyte-colony stimulating factor for neutropenia) per institutional standards.

Dose Modification Guidance

• Dose delays are the primary method for managing AEs in phase 2, Part 3 of the MonumenTAL-1 study. If a dose interruption is ≥28 days, treatment must be permanently discontinued unless continuation is agreed in consultation with the sponsor after a review of safety and efficacy. Repeat of step-up dose(s) and pretreatment medication may be required.
• Select criteria for a dose delay in phase 2, Part 3 related to hematologic AEs are:
  • Grade 4 hematologic AE (except lymphopenia) not directly related to the disease process
  • Grade 3 thrombocytopenia with bleeding
  • Febrile neutropenia (by default grade 3 or 4)
  • Grade 3 neutropenia with infection
• Criteria for dose delays due to TALVEY-related toxicities are as follows:
  • If toxicity occurs during the step-up dose:
    • The toxicity must resolve to baseline or grade ≤1 and there must be no evidence of serious bacterial, viral, or fungal infection before proceeding to the next step-up dose (if more than one step-up dose is to be administered) or to cycle 1 day 1.
    • One further attempt at step-up dosing is allowed within 28 days of any step-up dose.

CLINICAL DATA - MONUMENTAL-2 STUDY

MonumenTAL-2 (MMY1004; clinicaltrials.gov identifier NCT05050097) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with MM.^6,11-13

Study Design/Methods

• Key eligibility criteria:
  • Cohort D: measurable MM, NDMM, ECOG PS of 0-1, and transplant ineligible or not intended for transplant.^11,12
  • Cohort E: measurable MM; ≥2 prior LOTs, including a PI and an immunomodulatory drug; ECOG PS of 0-1; prior pomalidomide and prior TCR (CAR-T and BsAb) permitted; and no prior GPRC5D-targeted therapy.^11,13
• Primary endpoint for Cohort D and Cohort E: safety; AEs assessed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, except for CRS and immune effector cell-associated neurotoxicity syndrome, which were graded per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.^11-13 

Cohort D

Nooka et al (2024)¹² presented the incidence of hematologic AEs in the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months (range, 10.0-14.6) and the TALVEY 0.8 mg/kg Q4W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0).

Safety Results

• Hematologic treatment-emergent adverse events (TEAE) are summarized in Table: MonumenTAL-2 Study (Cohort D): Summary of Hematologic TEAEs (≥30%).

Cohort E

Searle et al (2024)¹³ presented the incidence of hematologic AEs in the TALVEY + pomalidomide cohort from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1).

Safety Results

• TEAEs related to hematologic AEs are summarized in Table: MonumenTAL-2 (Cohort E) Study: Hematologic AEs.
• Neutropenia was one of the most common AEs leading to pomalidomide dose reduction.

CLINICAL DATA - redirectt-1 STUDY - TALVEY + tecvayli COHORT

RedirecTT-1 (MMY1003; clinicaltrials.gov identifier: NCT04586426) is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of the combination of TALVEY and TECVAYLI in patients with RRMM.^3,7,14,15

Study Design/Methods

• Key inclusion criteria: relapsed or refractory or intolerant to established therapies including the last LOT, prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.^7,15
• Primary endpoints: dose limiting toxicity and ORR.^7,15

Cohen et al (2025)⁷ published the incidence of hematologic AEs from the phase 1 dose-escalation segment of the RedirecTT-1 study in the all-dose-level cohort at a median follow-up of 20.3 months (range, 0.5-37.1) and in the RP2R cohort at 18.2 months.

Safety Results

• At a data cutoff of March 15, 2024, the incidence of hematologic AEs was reported. See Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Hematologic AEs for additional details.^7,15
• Febrile neutropenia was reported in 12.8% of patients.^7,15

CLINICAL DATA - TRIMM-2 STUDY

TRIMM-2 (MMY1002; clinicaltrials.gov identifier: NCT04108195) ) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating DARZALEX FASPRO regimens in combination with bispecific TCR antibodies with or without pomalidomide in patients with RRMM.^2,16,17

Study Design/Methods

• Key eligibility criteria²:
  • Double refractory to a PI and an immunomodulatory drug or received ≥3 prior LOTs (including a PI and an immunomodulatory drug).
  • Treatment with an anti-CD38 monoclonal antibody (>90 days prior allowed), including anti-CD38 refractory patients.
  • Prior BsAb and CAR-T were allowed.
• Key primary endpoints²:
  • Part 1: identify the RP2D for each treatment combination.
  • Part 2: safety and tolerability at the selected RP2D of each treatment combination.
  • Antitumor activity.

Bahlis et al (2024)¹⁷ presented the incidence of hematologic AEs in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 15.8 months (range, 3.2-37.9) and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 17.5 months (range, 0.2-37.7).

Safety Results

• A total of 5.2% of patients (n=4) had febrile neutropenia and all events were reported in the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohort.
• The incidences of hematologic AEs are summarized in Table: TRIMM-2 Study (TALVEY + DARZALEX FASPRO + Pomalidomide Cohort): Hematologic AEs.

Dholaria et al (2023)² presented the incidence of hematologic AEs the TRIMM-2 study for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO 1800 mg Q4W cohort at a median follow-up of 16.8 months (range, 1.9-31.0) and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO 1800 mg Q4W cohort at a median follow-up of 15.0 months (range, 1.0-23.3).

Safety Results

• The incidence of hematologic AEs is summarized in Table: TRIMM-2 Study (TALVEY + DARZALEX FASPRO Cohort): Hematologic AEs.
• Cytopenias were generally confined to step-up and cycle 1-2 doses and resolved in most patients.

literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 18 February 2025.