Dr Berdeja on Optimal Referral Timing for CAR T-Cell Therapy in Multiple Myeloma

One of the things that we’re starting to find out as we have more BCMA-directed therapies [approved] is that the sequencing actually does matter.”

Jesús Berdeja, MD, director of Multiple Myeloma Research at Sarah Cannon Research Institute and Tennessee Oncology, discussed CAR T-cell therapy referral strategies for patients with multiple myeloma and optimal timing for this treatment modality within the greater treatment paradigm.

For patients with multiple myeloma, 2 BCMA-directed CAR T-cell therapies are currently approved by the FDA. On April 5, 2024, ciltacabtagene autoleucel (cilta-cel; Carvykti) was approved for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and who are refractory to lenalidomide (Revlimid). On the same day, the regulatory agency approved idecabtagene vicleucel (ide-cel; Abecma) for the treatment of adult patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including an IMiD, a PI, and an anti-CD38 monoclonal antibody. These indications built upon the initial approvals of cilta-cel and ide-cel, where they were indicated for patients with relapsed/refractory disease following 4 or more prior lines of therapy.

Berdeja emphasized that referral to specialized centers remains essential for patients being considered for CAR T-cell therapy, particularly as these therapies have moved earlier in the treatment paradigm for multiple myeloma, including the second-line setting. He noted that with the growing availability of other BCMA-directed options, such as bispecific antibodies and antibody-drug conjugates, sequencing has become a clinically meaningful issue for patients with relapsed/refractory disease.

From Berdeja’s perspective, optimizing outcomes hinges on thoughtful upfront planning. He suggested that for patients eligible for multiple BCMA-targeted approaches, CAR T-cell therapy should generally be prioritized first. He explained that exposure to other BCMA-directed therapies may compromise the efficacy of treatment with CAR T-cell therapy in a later line.

Importantly, Berdeja underscored that the timing of referral can directly affect patient outcomes, and as CAR T-cell therapy is weighed with other options, it remains vital for community oncologists to engage with specialized centers to help identify patients as candidates for CAR T-cell therapy and optimize the timing of administration.