Exploring Bispecific Combinations: REDIRECTT ASCO 2025 Highlights
An expert discusses that combining the bispecific antibodies teclistamab and talquetamab has shown promising efficacy and manageable toxicity in heavily pretreated multiple myeloma patients—including those with extramedullary disease—offering a compelling dual-targeted option for high-risk cases while allowing flexibility in sequencing for slower-progressing disease.
A recent clinical trial explored the combination of two bispecific antibodies—teclistamab, which targets BCMA, and talquetamab, which targets GPRC5D—in patients with relapsed/refractory multiple myeloma. Both agents individually have strong efficacy, but this study aimed to assess their combined impact, particularly in high-risk patients. The treatment protocol used a step-up dosing strategy, eventually spacing doses to every 4 weeks in patients who responded. The trial enrolled heavily pretreated patients, many with extramedullary disease, and demonstrated an overall response rate of approximately 80%, with over half achieving stringent complete responses.
Importantly, the combination proved highly effective even in the challenging subset of patients with extramedullary disease. Among these patients, many had already received multiple prior lines of therapy, including CAR T-cell therapy. The combination still yielded a nearly 80% response rate, and 75% of patients had durable responses at 9 months. The progression-free survival rate was 64% at that time point. These results are noteworthy given how difficult it is to treat patients with disease that extends beyond the bone marrow, and the data suggest a real benefit from dual-targeted therapy in this population.
Toxicities were largely manageable. Hematologic adverse events were common but expected, and typically handled with supportive care. Cytokine release syndrome was mostly low grade and occurred early in treatment. Talquetamab-specific adverse effects like taste changes, weight loss, and minor skin or nail changes were also observed. Infections were reported in about half of patients, but most were not severe. Overall, the combination appears promising, especially for patients with rapidly progressing or high-risk disease who may not be candidates for immediate CAR T therapy. However, for patients with slower disease, single-agent therapy may still be a more appropriate initial approach, with the option to reserve other agents for later use.
