Trials Evaluating Bispecific Antibodies in Earlier Therapy Lines Show Promise

CAR T-cell therapies, BCMA and GPRC5D bispecific antibodies, and cereblon E3 ligase modulators (CELMoDs) all have the potential to impact clinical practice for multiple myeloma, according to Surbhi Sidana, MD.

CancerNetwork® spoke with Sidana, associate professor and hematologist of the Department of Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy at Stanford University, about the results from the phase 1/2 LINKER-MM1 trial (NCT03761108) published in the Journal of Clinical Oncology, in which investigators assessed the efficacy and safety of linvoseltamab in patients diagnosed with relapsed/refractory multiple myeloma.1 The interview followed the recent FDA decision to give linvoseltamab a complete response letter for this application due to a third party manufacturing site issue.

Sidana stated that the current landscape of multiple myeloma treatment was exciting, citing multiple FDA approvals for CAR T-cell therapies and bispecific antibodies in recent years. Furthermore, she listed numerous therapies with the potential for FDA approval, including linvoseltamab, as well as the CELMoDs iberdomide and mezigdomide, and the monoclonal antibody belantamab mafodotin (Blenrep), which was initially approved and then withdrawn following FDA recommendation.Sidana concluded by asserting that bispecifics were being evaluated in earlier lines of therapy for multiple myeloma and that trial data affirming the efficacy of early-line bispecifics would help enable their use in clinical practice.

Transcript:

We are living in very exciting times in multiple myeloma. Over the last 3 to 4 years, we have had FDA approvals for 2 CAR [T-cell therapies], ide-cel (Abecma) and cilta-cel (Carvykti), that target BCMA; 3 bispecific antibodies, 2 that target BCMA, teclistamab-cqyv (Tecvayli) and elranatamab-bcmm (Elrexfio); and another that targets GPRC5D, talquetamab-tgvs (Talvey). Now we have other BCMA bispecifics, including linvoseltamab, that may get approved in the near future.

[There are] many other targets in development, both for bispecifics and CAR T, and also other drugs, like CELMoDs iberdomide and mezigdomide, [that] have shown promising data. We also had belantamab mafodotin (Blenrep), which was initially FDA approved. The approval was withdrawn; the accelerated approval was withdrawn based on a phase 3 study.

Another phase 3 study shows very promising data that was presented in the summer meetings in 2024, so this is a very exciting landscape—not only for the approval of new agents in late relapse, but also for earlier line approval of agents like CAR T. Over the summer, we had early-line approval of both cilta-cel, after 1 prior line of therapy in [lenalidomide (Revlimid)]-refractory patients, and ide-cel after 2 prior lines of therapy. Bispecifics are being investigated in earlier lines over the next couple of years. As those trial data come in, we would expect, hopefully to get those moved into earlier lines.

Reference

Bumma N, Richter J, Jagannath S, et al. Linvoseltamab for treatment of relapsed/refractory multiple myeloma. J Clin Oncol. Published June 16, 2024. doi:10.1200/JCO.24.01008