Dr Ailawadhi on the Potential Sequencing of Bispecific Antibodies in Multiple Myeloma

Sikander Ailawadhi, MD, medical oncologist, Department of Hematology, CAR T-Cell Therapy Program, Mayo Clinic, discusses key considerations for the potential sequencing of bispecific antibodies and other BCMA-directed therapies in multiple myeloma.

There are currently 3 FDA approved bispecific antibodies available for patients with multiple myeloma: teclistamab-cqyv (Tecvayli), elranatamab-bcmm (Elrexfio), or talquetamab-tgvs (Talvey). The first 2 agents target BCMA, while talquetamab targets GPRC5D. All 3 agents have demonstrated similar efficacy and safety profiles.

The optimal sequencing of both bispecific antibodies and other BCMA-targeted agents has become a critical consideration when determining treatment approaches in myeloma, Ailawadhi begins. However, there is uncertainty when determining whether these agents can be still administered to patients following disease progression on a prior BCMA-targeted therapy, or if they should only be administered once, he states. Existing data have been presented for these drugs in both previously untreated patients receiving BCMA-directed therapy and those who have received prior treatment with a BCMA-directed agent, with this drug class demonstrating efficacy in both scenarios, Ailawadhi reports.

Drawing a parallel with CAR T-cell therapy, favorable outcomes are observed when CAR T-cell therapy is administered to patients without prior exposure to a BCMA-targeted agent, Ailawadhi continues. However, the magnitude of benefit seen with CAR T-cell therapy is reduced in patients who have undergone previous BCMA-directed therapy, he says. The optimal strategy, therefore, involves considering CAR T-cell therapy as the initial BCMA-directed approach for eligible patients, as this maximizes the potential benefits, Ailawadhi explains.

In contrast, bispecific antibodies maintain their efficacy even in patients with a history of BCMA-directed therapy, Ailawadhi says, adding that there is a comparatively smaller decline in response compared to CAR T-cell therapy in similar settings. Overall, a more nuanced understanding of sequencing and treatment strategies contributes to informed decision-making in the evolving landscape of multiple myeloma, Ailawadhi concludes. Trials seeking to compare these standard-of-care multiple myeloma regimens are ongoing in this population.