Dr Krishnan on T-Cell Therapies and Novel Targets Reshaping the Myeloma Treatment Landscape

"The field of myeloma is advancing so rapidly, the use of T-cell–directed therapies is evolving in the sense of combination therapies; [therefore]…sequencing in the future will actually become more complicated."

Amrita Krishnan, MD, director of the Judy and Bernard Briskin Center for Multiple Myeloma Research at City of Hope, outlines key therapeutic developments in multiple myeloma in recognition of Myeloma Awareness Month, which occurs every year in March, with a particular focus on emerging targets and evolving strategies in T-cell–directed therapy.

Krishnan notes that although BCMA remains the most clinically validated target in multiple myeloma, the treatment landscape is rapidly expanding to include agents directed against GPRC5D and other novel targets. T-cell–redirecting therapies, such as bispecific antibodies and CAR T-cell therapies, continue to gain traction, with ongoing trials exploring their use in earlier lines of therapy and in combination with established agents.

This progress reflects a broader shift in myeloma management toward immunotherapy-based approaches, Krishnan explains. Combinatorial strategies are being actively investigated to deepen responses and overcome resistance, and greater attention is being paid to sequencing—particularly in patients previously exposed to BCMA-targeted therapies. As novel agents move closer to approval, therapeutic decision-making is expected to become more nuanced, requiring individualized strategies based on patient characteristics, disease biology, and prior treatment exposure.

Krishnan highlights that the introduction of GPRC5D-targeting agents—both CAR T-cell therapies and ADCs—offers an alternative for patients who have progressed on BCMA-directed treatment. This diversification in target selection reflects the need for new mechanisms of action to sustain durable disease control in the relapsed/refractory setting.

Looking ahead, Krishnan emphasizes that T-cell–redirecting therapies will likely form the backbone of future multiple myeloma treatment paradigms. As these agents become more widely available and their use better defined, attention will shift to optimizing treatment sequencing, managing toxicities, and ensuring broader access across both academic and community settings.

In the context of Myeloma Awareness Month, Krishnan stresses the importance of education, awareness, and ongoing clinical research to further refine therapeutic approaches. As more patients live longer with the disease, a continued focus on innovation and precision in care delivery will be essential to improve long-term outcomes.