Relapsed/Refractory Multiple Myeloma: Rationale and Design of the MonumenTAL-3 Study

Description - Dr. Ajai Chari and Dr. Rahul Banerjee discuss the clinical rationale behind the phase 3 MonumenTAL-3 study and its role in confirming the benefit-risk profile of talquetamab in relapsed/refractory multiple myeloma (RRMM). Following the accelerated approval of talquetamab based on MonumenTAL-1, the faculty review the need for a registrational study capable of evaluating talquetamab in earlier lines of therapy and in combination with established agents. Dr. Banerjee explains the scientific rationale for combining talquetamab with daratumumab and pomalidomide, highlighting the potential immunomodulatory effects of these agents beyond their direct antimyeloma activity. The discussion also examines how findings from the TRIMM-2 study helped establish the feasibility, safety, and preliminary efficacy of talquetamab-based combinations, including in heavily pretreated and anti-CD38–exposed patient populations. Dr. Chari and Dr. Banerjee review key observations regarding response durability, toxicity management, and combination strategies that ultimately informed the design and treatment arms evaluated in the MonumenTAL-3 trial.