Dr Zonder on CAR T-cell Therapy Vs Bispecific Antibodies in Relapsed/Refractory Myeloma

Jeffery Zonder, MD, leader, the Multiple Myeloma Sub-committee, the Barbara Ann Karmanos Cancer Institute, professor of medicine, the Departments of Hematology and Oncology, Wayne State University School of Medicine, discusses the process of choosing between CAR T-cell therapy and bispecific antibody approaches for the treatment of patients with relapsed/refractory multiple myeloma.

Two CAR T-cell therapies are currently approved by the FDA for patients with multiple myeloma: idecabtagene vicleucel (ide-cel; Abecma), which was approved in March 2021, and ciltacabtagene autoleucel (cilta-cel; Carvykti), which was approved in February 2022. Additionally, in October 2022, the regulatory agency granted accelerated approval to the bispecific antibody teclistamab-cqyv (Tecvayli) for adult patients with relapsed or refractory multiple myeloma. All 3 treatments are indicated for patients who have received at least 4 prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Notably, both ide-cel and cilta-cel are BCMA-targeted CAR T-cell therapies, and teclistamab targets both BMCA and CD3.

Among BCMA-targeted therapies, CAR T-cell therapy has the advantage of being administered at as a single infusion, and both ide-cel and cilta-cel have been associated with high response rates, Zonder begins. However, access to CAR T-cell therapy remains an obstacle for this patient population, Zonder says, adding that their is a waiting period for treatment slots at most cancer centers that can administer CAR T-cell therapy. Additionally, after T cells are collected and sent for manufacturing, there is another waiting period prior to their administration, Zonder continues. These time constraints may make CAR T-cell therapy unfeasible for some patients who fall under the approved indication, since a patient who has rapidly progressing disease after 4 prior lines of therapy may not be able to wait for CAR T-cell therapy, Zonder says. Oftentimes, bridging therapy will be needed keep the disease at bay during the waiting process.

Although teclistamab, in particular, is administered weekly, bispecific antibodies are an off-the-shelf therapy, so the treatment process can be started right away. Although response rates are not as high for bispecific antibodies compared with CAR T-cell therapy, these agents represent a significant leap forward compared to previous treatment options in this setting, Zonder says. Choosing between CAR T-cell therapy and a bispecific antibody comes down to how urgently the therapy is needed for a patient, Zonder concludes.