Talquetamab Demonstrates Preserved Activity in MonumenTAL-1–Ineligible Patients With Relapsed/Refractory Myeloma

Talquetamab-tgvs (Talvey) yielded similar responses in patients with relapsed/refractory multiple myeloma regardless of whether they would have met the eligibility criteria of the phase 1/2 MonumenTAL-1 trial (NCT03399799; NCT04634552), and progression-free survival (PFS) and overall survival (OS) were longer among patients who would have been trial-ineligible, according to findings from a real-world retrospective analysis presented in a poster session at the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting.¹

The large majority of patients treated in routine practice would not have qualified for the registrational trial, most often because of prior BCMA-directed or T-cell–redirecting therapy.

Among patients treated at Moffitt Cancer Center (n = 95), 85.3% would not have met MonumenTAL-1 eligibility criteria, and 14.7% would have. The median PFS was 18.2 months among patients who would not have met the criteria (n = 81) vs 9.1 months among those who would have (n = 14; log-rank P = .005). The median OS was 22.5 months vs 11.2 months, respectively (log-rank P = .009). The overall response rate (ORR), the study's primary end point, was similar between the 2 groups, according to the investigators.

"ORR was preserved across eligibility groups; PFS and OS were unexpectedly longer among patients who would not have met trial criteria," lead study author Juan Carlos Ramirez, MD, an internal medicine resident at the University of South Florida Morsani College of Medicine in Tampa, and coauthors wrote in a poster presentation of the data. The investigators added that the survival differences are hypothesis-generating given the marked imbalance between the groups and potential physician treatment selection bias.

In August 2023, the FDA granted accelerated approval to talquetamab for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.² This decision was backed by data from MonumenTAL-1.

How was the study designed?

Talquetamab is a GPRC5D × CD3 bispecific T-cell engager that demonstrated activity in heavily pretreated relapsed/refractory multiple myeloma in MonumenTAL-1.¹ According to the investigators, its efficacy among patients who would have been excluded from that trial, particularly after prior BCMA-directed therapy, remains clinically relevant as T-cell–redirecting therapies are used earlier in the treatment course.

This single-center retrospective cohort study included patients with relapsed/refractory multiple myeloma who received talquetamab at Moffitt Cancer Center in Tampa, Florida, between May 2023 and November 2025; patients who received talquetamab as bridging to CAR T-cell therapy were excluded.

MonumenTAL-1 eligibility was retrospectively adjudicated using published criteria, and responses were assessed per International Myeloma Working Group (IMWG) criteria.

The primary end point was ORR; secondary end points included PFS, OS, duration of response, and safety. Time-to-event outcomes were analyzed using Kaplan-Meier methods and log-rank tests, and ORR was compared using Fisher's exact test.

The median age was 67 years, and patients had received a median of 7 prior lines of therapy. The median follow-up was 9.7 months. Additionally, 96.8% of patients (n = 95) had an ECOG performance status of 2 or lower, and 74.7% had a performance status of 0 or 1.

Among patients who would not have met eligibility criteria, reasons for ineligibility included prior BCMA-directed or T-cell–redirecting therapy (n = 55; 67.9%), neutropenia (n = 24; 29.6%), renal dysfunction (n = 20; 24.7%), anemia (n = 17; 21.0%), and thrombocytopenia (n = 15; 18.5%). Patients could meet more than 1 ineligibility criterion.

Did prior BCMA-directed therapy affect outcomes?

In a sequencing analysis, 84 patients had received prior BCMA-directed therapy, and 11 had not. The median PFS was 16.9 months among patients with prior BCMA exposure vs 12.5 months among those without (log-rank P = .193). The median OS was 22.3 months vs 13.4 months, respectively (log-rank P = .137). The investigators reported no statistically significant difference in PFS or OS by prior BCMA exposure.

What did the safety analysis show?

Cytokine release syndrome (CRS) occurred in 40.0% of patients (n = 95), with a median CRS grade of 2. Grade 3 or higher CRS occurred in 3.2% of patients (3/95), including 2 grade 3 events and 1 grade 4 event. The mean CRS-related hospitalization lasted 2.9 days.

Prophylactic tocilizumab (Actemra) was administered to 38 patients. Sixteen patients underwent outpatient step-up initiation, 81.3% of whom received prophylactic tocilizumab.

References

1. Ramirez J, Darji R, Wright C, et al. Real-world outcomes of talquetamab in MonumenTAL-1 trial-ineligible versus trial-eligible patients with relapsed/refractory multiple myeloma (RRMM). Presented at: 2026 Society of Hematologic Oncology (SOHO) Annual Meeting; September 9-12, 2026; Houston, TX. Abstract [not reported].
2. U.S. FDA approves Talvey (talquetamab-tgvs), a first-in-class bispecific therapy for the treatment of patients with heavily pretreated multiple myeloma. News release. Janssen. August 10, 2023. Accessed October 5, 2023. https://www.janssen.com/us-fda-approves-talveytm-talquetamab-tgvs-first-class-bispecific-therapy-treatment-patients-heavily