Dr Usmani on the Risk-Benefit Profile of Cilta-Cel in Relapsed/Refractory Multiple Myeloma

Saad Z. Usmani, MD, MBA, FACP, FASCO, chief, Myeloma Service, Memorial Sloan Kettering Cancer Center, discusses the FDA’s Oncologic Drugs Advisory Committee (ODAC) review of the risk-benefit profile of ciltacabtagene autoleucel (cilta-cel; Carvykti) in relapsed/refractory multiple myeloma, which occurred prior to the agent's FDA approval.

The FDA approved cilta-cel for the treatment of adult patients with relapsed/refractory multiple myeloma following 1 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide (Revlimid), on April 5, 2024. The decision was supported by topline data from the phase 3 CARTITUDE-4 trial (NCT04181827) which demonstrated a 59% reduction in the risk of disease progression or death in patients treated with cilta-cel (n = 208) vs patients treated with a standard of care regimen (n = 211).

Prior to the FDA's approval of cilta-cel, the FDA's ODAC voted in favor of cilta-cel for patients with early relapsed/refractory myeloma on March 15, 2024, Usmani begins. The key issue scrutinized during this process was the occurrence of early deaths observed in patients receiving cilta-cel while on bridging therapy compared with patients receiving a standard triplet regimen, he explains. There was an imbalance noted, with 7 patients in the cilta-cel arm vs 1 patient in the control arm experiencing disease-related deaths during this period, Usmani details. It was important to evaluate if this was connected to cilta-cel, but it was determined to be unrelated, underscoring the heterogeneous and aggressive nature of disease progression events in myeloma, he reports.

Despite these events, the overall survival (OS) signal observed favored cilta-cel, Usmani notes. Although these data did not reach statistical significance required by the FDA, they indicate that OS outcomes were not worse in the cilta-cel arm, Usmani states. The decision provided more assurance to physicians, especially after considering patient perspectives advocating for this treatment option and the opportunity for meaningful discussions with their healthcare providers during their disease course, he concludes.