Dr Banerjee on the Benefit of Bispecific Antibody Dose Reduction in Multiple Myeloma

Rahul Banerjee, MD, FACP, assistant professor, Clinical Research Division, Fred Hutch Cancer Center; member, the International Myeloma Working Group; assistant professor, Division of Hematology and Oncology, University of Washington, discusses notable clinical benefits that may be derived from reducing the dosing of bispecific antibodies in the treatment of patients with multiple myeloma.

Dose reduction of bispecific antibodies can provide advantages beyond a decrease in toxicities, Banerjee begins. Although not fully confirmed, preclinical research suggests that bispecific antibodies might lead to T-cell exhaustion, he explains. Bispecific antibodies direct T cells toward a specific target, diverting them from their natural course. This continuous redirection could result in T-cell exhaustion, especially in the setting of multiple myeloma, where T cells face repeated attacks on numerous cancer cells, Banerjee reports. However, there some data suggest that a treatment-free interval could rejuvenate T cells and prevent their exhaustion in patients undergoing bispecific antibody treatment, he adds.

Interestingly, this research may pose a challenge to the longstanding dose selection paradigm, which is typically centered on administering the maximum tolerated dose, he continues. Investigators may discover that dose reduction is not only safer and less toxic over time but may ultimately enhance efficacy. Early studies of dose reduction with talquetamab-tgvs (Talvey) hint at this possibility, he adds. Whether this improved tolerance will allowpatients to remain on treatment longer or the reduced dosage prevents T-cell exhaustion remains unclear. Nonetheless, this approach warrants further investigation, Banerjee emphasizes.

As oncologists’ understanding of bispecific antibodies in multiple myeloma management continues to evolve, their optimal use remains in constant flux, Banerjee continues. Although this may seem frustrating, it reflects substantialprogress, he says. The shifting landscape of this treatment paradigm is a welcome development, offering hope for improved therapeutic strategies, Banerjee concludes.