TALVEY - Use as Monotherapy in Patients With Extramedullary Disease

SUMMARY

• Data included in this response is limited to evaluations of TALVEY administered as monotherapy in patients with relapsed or refractory multiple myeloma (RRMM) with extramedullary disease (EMD).
• Johnson & Johnson does not recommend the use of TALVEY in a manner inconsistent with the approved labeling.
• MonumenTAL-1 is an ongoing, open-label, phase 1/2 study evaluating the efficacy and safety of TALVEY in patients with RRMM after ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).^1-3
  • Chari et al (2025)^3,4 published a post hoc analysis with a longer-term follow-up that evaluated the efficacy and safety of TALVEY at the recommended phase 2 dose (RP2D) at a median follow-up of 25.6 months (interquartile range [IQR], 8.5-25.9) for the 0.4 mg/kg subcutaneous (SC) weekly (QW) cohort, 19.4 months (IQR, 9.2-20.7) for the 0.8 mg/kg SC every other week (Q2W) cohort, and 16.8 months (IQR, 7.6-18.7) for the prior T-cell redirection therapy (TCR)-exposed cohort from phases 1 and 2 of the MonumenTAL-1 study. The overall response rate (ORR) in the extramedullary plasmacytoma (≥1) subgroup was 48% for the 0.4 mg/kg SC QW cohort and 41% for the 0.8mg/kg SC Q2W cohort.
  • Rasche et al (2024)⁵ presented long-term follow-up efficacy and safety results from the MonumenTAL-1 study at a median follow-up of 29.8 months for the 0.4 mg/kg SC weekly QW cohort, 23.4 months for the 0.8 mg/kg SC Q2W cohort, and 20.5 months for the prior TCR therapy-exposed cohort. The ORR in the extramedullary plasmacytoma (≥1) subgroup was 48.5%, 41.5%, and 44.0% for the 0.4 mg/kg SC QW, 0.8 mg/kg SC Q2W, and prior TCR therapy-exposed cohorts, respectively.
  • Krishnan et al (2023)⁶ presented subgroup analyses of the efficacy and safety results from the MonumenTAL-1 study phases 1/2 in patients who received TALVEY at the recommended phase 2 doses (RP2Ds) of 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W, including those who were naïve or exposed to TCR therapy. At a median follow-up of 18.4 months for the 0.4 mg/kg SC QW EMD subgroup, the ORR was 48.5%. At a median follow-up of 12.1 months for the 0.8 mg/kg SC Q2W EMD subgroup, the ORR was 43.2%.
• Afrough et al (2025)⁷ presented results from a multicenter retrospective study conducted across 15 United States (US) centers that evaluated outcomes by soft tissue plasmacytoma (STP) type in patients with RRMM treated with TALVEY.
• Other relevant literature has been identified in addition to the data summarized above.^8,9 

CLINICAL DATA - mONUMENTAL-1 STUDY

MonumenTAL-1 (NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^10,11

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 3 cohorts^2,12:

• TCR naive: 0.4 mg/kg SC QW, not previously exposed to TCR such as chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAbs; prior B-cell maturation antigen [BCMA] antibody-drug conjugate [ADC] allowed).
• TCR naive: 0.8 mg/kg SC Q2W, not previously exposed to TCRs (prior BCMA ADC allowed).
• Prior TCR-exposed: 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 criteria³:
  • ≥18 years of age, measurable MM per International Myeloma Working Group (IMWG) criteria.
  • ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 mAb.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.

Chari et al (2025)^3,4 published a post hoc analysis with a longer-term follow-up to evaluate the efficacy and safety results in patients receiving TALVEY in phases 1 and 2 of the MonumenTAL-1 study. The efficacy results for the subgroup of patients with baseline extramedullary disease are summarized below.

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

• A total of 143 patients were included in the 0.4 mg/kg SC QW cohort, 154 patients in the 0.8 mg/kg SC Q2W cohort, and 78 patients in the prior TCR-exposed cohort.
• The median duration of follow-up was 25.6 months (IQR, 8.5-25.9) for the 0.4 mg/kg SC QW cohort, 19.4 months (IQR, 9.2-20.7) for the 0.8 mg/kg SC Q2W cohort, and 16.8 months (IQR, 7.6-18.7) for the prior TCR-exposed cohort.

Efficacy

• At a data cutoff of October 11, 2023, ORR was 74% in the 0.4 mg/kg SC QW cohort and 69% in the 0.8 mg/kg SC Q2W cohort.
• ORR in the baseline extramedullary plasmacytoma subgroup is detailed in Table: MonumenTAL-1 Study: ORR in Patients with Baseline Extramedullary Disease.
• PFS in the baseline EMD subgroup is presented in Table: MonumenTAL-1 Study: Median PFS in Patients With Baseline Extramedullary Disease.

Rasche et al (2024)⁵ presented longer term follow-up efficacy and safety results in patients receiving TALVEY in the MonumenTAL-1 study. The efficacy results of the latest follow-up are summarized below.

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

• A total of 143 patients were included in the 0.4 mg/kg SC QW cohort, 154 patients in the 0.8 mg/kg SC Q2W cohort, and 78 patients in the prior TCR-exposed cohort.
• The median duration of follow-up was 29.8 months for the 0.4 mg/kg SC QW cohort, 23.4 months for the 0.8 mg/kg SC Q2W cohort, and 20.5 months for the prior TCR cohort.

Efficacy

• At a data cutoff of January 29, 2024, ORR was 74.1% in the 0.4 mg/kg SC QW cohort, 69.5% in the 0.8 mg/kg SC Q2W cohort, and 66.7% in the prior TCR-exposed cohort. ORR in the extramedullary plasmacytoma subgroup is detailed in Table: MonumenTAL-1 Study: ORR in the Extramedullary Plasmacytomas Subgroup.

Krishnan et al (2023)⁶ evaluated the efficacy and safety of TALVEY in key high-risk and BCMA-exposed subgroups of patients from phases 1/2 of the MonumenTAL-1 study.

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

• Overall, 143 patients in the 0.4 mg/kg SC QW cohort and 145 patients in the 0.8 mg/kg SC Q2W cohort were included in the subgroup analysis. Baseline demographic characteristics in the 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W cohorts across the EMD subgroup is presented in Table: MonumenTAL-1 Study: Baseline Demographic Characteristics in EMD Subgroup.

Efficacy

EMD Subgroup

• The median follow-up and ORR in the EMD subgroup of the 0.4 mg/kg QW and 0.8 mg/kg Q2W dosing cohorts is presented in Table: MonumenTAL-1 Study: ORR in EMD Subgroup.
• Select efficacy outcomes in the EMD subgroup in the 0.8 mg/kg SC Q2W cohort are summarized in Table: MonumenTAL-1 Study: Efficacy Outcomes in the EMD Subgroup in the 0.8 mg/kg SC Q2W Cohort.

Safety

• Adverse events (AEs) observed in the RP2Ds of the 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W EMD subgroup are summarized in Table: MonumenTAL-1 Study: Summary of AEs in the EMD Subgroup.
  • Rates of AEs (dysgeusia, nail AEs, and skin AEs) were lower in EMD subgroup in the 0.4 mg/kg SC QW cohort.
  • Rates of infection were lower in the EMD subgroup in both cohorts.

Real-world Analyses

Afrough et al (2025)⁷ presented results from a multicenter retrospective study conducted across 15 US centers that evaluated outcomes by soft tissue plasmacytoma (STP) type in patients with RRMM treated with TALVEY.

Study Design/Methods

• This multicenter retrospective study included 463 patients with RRMM treated with TALVEY across 15 US centers through December 2024.
• Patients were categorized by STP status at TALVEY initiation as EMD (lesions not contiguous with bone), paraskeletal disease (PSK; bone-contiguous), EMD + PSK, and no STP.
• Patients who received TALVEY as a bridge-to-CAR-T therapy (n=103) were censored at CAR-T infusion if disease progression had not occurred.
• Time-to-event endpoints were calculated from TALVEY step-up dosing (SUD) using Kaplan-Meier/Cox models.

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

• Baseline characteristics presented in the Table: Baseline Demographic and Disease Characteristics by STP Status.
• In the EMD population (combined EMD and EMD + PSK subgroups), 81 patients (69%) had visceral involvement, and 85 patients (73%) had multiple lesions at TALVEY initiation.
• Other features, including prior BCMA- or GPRC5D-directed therapy, plasma cell leukemia (PCL; ≥5% circulating plasma cells at TALVEY initiation), and penta-refractory disease were reported at similar rates across the STP subgroups.

Efficacy

• Efficacy outcomes are summarized in Tables: Response Rates by STP Status, Survival Outcomes by STP Status, and Multivariable Analyses of PFS and OS.

Safety

• The incidence and severity of cytokine release syndrome (CRS) were similar across the STP subgroups.
• No differences in the onset or duration of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were observed across the STP subgroups.
• Safety outcomes are summarized in Table: Summary of Select Safety Outcomes by STP Status.
• Across the STP subgroups, deaths were primarily disease related (P=0.6).

Literature Search

A literature search of Ovid MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 04 August 2026.