Phase 3 MonumenTAL-6 Trial Demonstrates Significant Survival Benefit With Dual-Bispecific Immunotherapy in Relapsed or Refractory Multiple Myeloma

Clinical Summary: 

• Design/Population: This global phase 3 trial evaluated teclistamab plus talquetamab and talquetamab plus pomalidomide versus investigator's choice of standard therapy in patients with relapsed or refractory multiple myeloma who had received 1 to 4 prior lines of therapy, including an anti-CD38 antibody and lenalidomide.
• Key Outcomes: Both investigational regimens significantly improved progression-free survival compared with standard therapy, with teclistamab plus talquetamab also reducing the risk of death by 62%. Safety profiles were consistent with the known profiles of the individual agents.
• Clinical Relevance: These findings support earlier use of bispecific antibody–based combinations in relapsed or refractory multiple myeloma and further evaluation of dual BCMA and GPRC5D targeting as an earlier-line treatment strategy.

Results from the phase 3 MonumenTAL-6 trial demonstrated that dual-bispecific immunotherapy with teclistamab plus talquetamab reduced the risk of disease progression or death by 89% and significantly improved overall survival (OS) compared with standard therapy in patients with relapsed or refractory multiple myeloma, supporting further evaluation of dual-antigen immunotherapy in earlier lines of treatment.

This global trial enrolled patients with relapsed or refractory multiple myeloma who had received 1 to 4 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. Patients were randomized to receive teclistamab plus talquetamab, talquetamab plus pomalidomide, or investigator's choice of elotuzumab, pomalidomide, and dexamethasone or pomalidomide, bortezomib, and dexamethasone. The primary end point was progression-free survival (PFS), as assessed by independent review. Key secondary end points included overall response rate (ORR), complete response or better, minimal residual disease-negative complete response, and OS.

At the first interim analysis, both investigational regimens met the primary end point. Teclistamab plus talquetamab reduced the risk of disease progression or death by 89% compared with investigator's choice therapy (hazard ratio [HR], 0.11; 95% confidence interval [CI], 0.08 to 0.16; P < .0001). Talquetamab plus pomalidomide reduced the risk by 73% (HR, 0.27).

Teclistamab plus talquetamab also significantly improved OS, reducing the risk of death by 62% compared with standard therapy (HR, 0.38). According to Johnson & Johnson, this represents the lowest hazard ratio reported among phase 3 studies evaluating bispecific antibody therapies in relapsed or refractory multiple myeloma.

The safety profiles of teclistamab plus talquetamab and talquetamab plus pomalidomide were consistent with the established safety profiles of the individual agents, and no new safety signals were reported.

Based on the strength of the interim findings, the independent data monitoring committee recommended unblinding the study at the first interim analysis. Full efficacy and safety data will be presented at a future scientific meeting and submitted to global health authorities. 

“These findings add to a growing body of Phase 3 evidence evaluating the survival outcomes associated with the early use of immunotherapy doublets in the treatment journey," stated Ajay K. Nooka, MD, Emory University School of Medicine, Atlanta, Georgia. "TECVAYLI and TALVEY together generated deep and durable responses, demonstrating what's possible by targeting BCMA and GPRC5D at the same time, and further reinforcing the potential of this off-the-shelf regimen to improve outcomes for patients across practice settings." 

Source: 

PR Newswire. TECVAYLI® + TALVEY® reduced the risk of disease progression or death by 89% and the risk of death by 62% in earlier-line relapsed/refractory multiple myeloma. Accessed on July 23, 2026. https://www.prnewswire.com/news-releases/tecvayli--talvey-reduced-the-risk-of-disease-progression-or-death-by-89-and-the-risk-of-death-by-62-in-earlier-line-relapsedrefractory-multiple-myeloma-302833309.html