Dr Delforge on the Rationale for CARTITUDE-4 in Lenalidomide-Refractory Myeloma

Michel Delforge, MD, PhD, professor, Faculty of Medicine, Department of Hematology, director, member, Leuven Cancer Institute, member, Senior Academic Staff, Council of the Faculty of Medicine, Council of the Department of Oncology, University Hospital Leuven, University of Leuven, discusses the background for conducting the phase 3 CARTITUDE-4 study (NCT04181827) in patients with lenalidomide (Revlimid)–refractory multiple myeloma. This investigation evaluated treatment with ciltacabtagene autoleucel (ciltacabtagene autoleucel; cilta-cel) compared with alternative approaches.

CARTITUDE-4 represents a pivotal study, as it was one of the first to investigate the effectiveness of a single infusion of a CAR T-cell therapy, cilta-cel, in comparison with standard of care (SOC) regimens for patients with relapsed or refractory multiple myeloma, Delforge begins. Typically, the SOC in this context involves combination therapies administered until disease progression occurs, he shares. Although many of these combination regimens demonstrate efficacy, the reality is that most patients will ultimately face disease relapse, along with the associated burden of ongoing treatment, Delforge states.

In the CARTITUDE-4 trial, cilta-cel was compared with 2 SOC regimens: one consisted of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone, and the other included daratumumab (Darzalex), pomalidomide, and dexamethasone, Delforge expands. Patients in this study had previously undergone at least 1 line of therapy and were refractory to lenalidomide, he says. The primary findings indicated that cilta-cel exhibited clear superiority over SOC regimens concerning various efficacy measures, including overall response rate, complete response rate, andprogression-free survival, as well as, according to the latest update, a significant improvement in overall survival, Delforge reports.

However, it is essential to acknowledge the study’s limitations, particularly regarding indirect comparisons, which often come with inherent challenges, he continues. The scientific community tends to be cautious about relying on indirect comparisons, as they can sometimes be used to support conclusions that are not particularly strong, according to Delforge. In the case of CARTITUDE-4, the comparisons serve a confirmatory role, providing clear evidence rather than merely attempting to validate less compelling claims, Delforge concludes.