Talquetamab and Cetrelimab Show Promising Efficacy in R/R Myeloma

In a groundbreaking study presented at the 2025 European Hematology Association (EHA) Congress, the combination of talquetamab-tgvs (Talvey) and cetrelimab has demonstrated significant safety and efficacy for patients suffering from relapsed/refractory multiple myeloma (R/R MM). This phase 1b TRIMM-3 trial, which included 44 participants, revealed promising results, indicating a 70.5% overall objective response rate (ORR) and a very good partial response or higher rate of 65.9%. This study provides hope for patients who have exhausted other treatment options, particularly those previously treated with bispecific antibodies.

The trial, led by Dr. Aurore Perrot, MD, PhD, an associate professor of hematology at the Centre Hospitalier Universitaire de Toulouse, France, observed that the median follow-up period was 11.5 months, with a remarkable median duration of response (DOR) of 16.8 months. Notably, the complete response (CR) rate stood at 6.8%, while the partial response (PR) rate reached 4.5%. These findings suggest that talquetamab may serve as a versatile combination partner, potentially enhancing the efficacy of PD-1 inhibitors like cetrelimab in this patient population, which often includes those with heavily pretreated disease.

The safety profile of the combination treatment also warrants attention. The most frequently reported adverse effects (AEs) included changes in taste (81.8%), skin reactions (70.5%), and infections (81.8%), though the majority of these were of low grade. The trial reported a 61.4% incidence of cytokine release syndrome (CRS), primarily grade 1 or 2, which is consistent with earlier studies on talquetamab. Importantly, the investigational treatment did not result in significant reductions in B-cell counts, suggesting a favorable immune response in patients.

Dr. Perrot emphasized the need for ongoing studies to further assess the combination’s impact on R/R MM, particularly regarding its long-term effects on patient outcomes and quality of life. Talquetamab, a bispecific antibody targeting GPRC5D, received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2023 for use in adults with R/R MM who had undergone at least four prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

The TRIMM-3 study's findings are anticipated to pave the way for future trials exploring the full potential of talquetamab and cetrelimab in treating multiple myeloma, a malignancy characterized by the proliferation of plasma cells in the bone marrow. As the global oncology community continues to seek effective therapeutic options for this challenging disease, the results from this trial represent a significant advancement in the field. The combination therapy may not only extend survival but also improve the quality of life for patients grappling with heavily pretreated multiple myeloma.