Dr Ailawadhi on Non-BCMA CAR T-Cell Therapies Under Investigation in Multiple Myeloma

Sikander Ailawadhi, MD, oncologist, Department of Hematology, CAR T-Cell Therapy Program, Mayo Clinic, discusses non-BCMA CAR T-cell therapies currently under investigation in multiple myeloma.

Despite the availability of BCMA-directed CAR T-cell therapies, the pursuit of non–BCMA-targeted treatment options remains crucial in advancing multiple myeloma care, Ailawadhi begins. CAR T-cell therapies targeting GPRC5D offer a promising alternative, he asserts. One such agent is the GPRC5D-targeted bispecific antibody talquetamab-tgvs (Talvey), Ailawadhi states. The agent is currently approved by the FDA for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. This agent demonstrated meaningful overall response rates in heavily pretreated patients who were not exposed to prior T-cell redirection therapy in the phase 2 MonumenTAL-1 trial (NCT04634552), which in turn supported this regulatory decision.

Ongoing research is also dedicated to developing CAR T-cell therapies directed against CD38, a marker currently targeted by the immunotherapy agents daratumumab (Darzalex) and isatuximab (Sarclisa), Ailawadhi continues. Additionally, the exploration of CAR products using non-T-cell cellular options includes CAR natural killer (NK) cells and CAR macrophages, Ailawadhi notes. Another target of interest is SLAMF7, addressed by the immunotherapy elotuzumab (Empliciti), he adds.

In addition, the field of multiple myeloma is witnessing the emergence of allogeneic CAR T-cell therapies, Ailawadhi says. This therapeutic option utilizes T cells from a donor instead of the patient's own T cells, Ailawadhi describes. Allogeneic CAR T-cell therapies offer patients several advantages due to their off-the-shelf nature, including streamlining the treatment process by eliminating the need for personalized manufacturing, Ailawadhi states.

Ultimately, diversifying targets for drug development, utilizing allogeneic CAR T-cell therapy, and exploring different cellular components like CAR NK cells all contribute to the comprehensive and evolving landscape of multiple myeloma therapeutics, Ailawadhi concludes.