Dr Bal on Unmet Needs With CAR T-cell Therapy in Multiple Myeloma

Susan Bal, MD, assistant professor, Hematology, Medical Oncology, University of Alabama at Birmingham (UAB), UAB Health, discusses unmet needs with CAR T-cell therapy in multiple myeloma.

Improving the durability of responses for patients with multiple myeloma who receive CAR T-cell therapy remains an area of need, Bal begins. Although CAR T-cell therapy can elicit early responses that deepen within the first month of treatment, patients continue to relapse, and a plateau has not been observed on progression-free survival curves, Bal adds.

Additionally, the 2 CAR T-cell therapies currently approved by the FDA—idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti)—are both BCMA-targeted agents. Treatment strategies for patients who relapse following one of these CAR T-cell therapies still need to be improved, and exploring other targets for CAR T-cell therapy in multiple myeloma, such as GPRC5D, remains a key area of interest, Bal says. She notes that data presented in 2022 on MCARH109, a CAR T-cell therapy targeting the GPRC5D, showed that the CAR T-cell therapy elicited remissions in patients with relapsed/refractory multiple myeloma.

As agents directed at different targets emerge, understanding how to sequence these therapies will be vital, Bal says. For example, patients who have received prior BCMA-directed CAR T-cell therapy have been shown to respond to an agent targeting GPRC5D, she says.

Notably, the BCMA- and CD3-targeted bispecific antibody teclistamab-cqyv (Tecvayli) was approved by the FDA in October 2022 for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, which is the same indication as ide-cel and cilta-cel.

Since teclistamab also targets BCMA, questions remain regarding the sequencing of the bispecific antibody and CAR T-cell therapy, and future investigations will need to look at the kinetics of how patients perform when they are first treated with CAR T-cell therapy vs a bispecific antibody, Bal concludes.