Dr Usmani on the Design of the CARTITUDE-4 Trial in Multiple Myeloma

Saad Z. Usmani, MD, MBA, FACP, FASCO, chief, Myeloma Service, Memorial Sloan Kettering Cancer Center, discusses the design of the phase 3 CARTITUDE-4 trial (NCT04181827) which investigated the role of ciltacabtagene autoleucel (cilta-cel; Carvykti) in patients with relapsed/refractory multiple myeloma.

On April 5, 2024, the FDA approved cilta-cel 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 and an immunomodulatory agent, and who are refractory to lenalidomide (Revlimid); findings from the CARTITUDE-4 trial support this regulatory decision.

In the CARTITUDE-4 trial, patients who had undergone 1 to 3 prior lines of treatment were enrolled, Usmani begins. They were then randomly allocated to either receive cilta-cel in the interventional arm or have their treatment determined by their physician from a selection that included pomalidomide, bortezomib, and dexamethasone, or daratumumab, pomalidomide, and dexamethasone in the standard-of-care (SOC) arm.

The primary objective of the study was to assess progression-free survival (PFS), a crucial measure in evaluating the efficacy of treatments for multiple myeloma, he reports. Notably, the study demonstrated a significant advantage in PFS favoring cilta-cel, with a median PFS that has yet to be reached. Conversely, patients in the SOC arm experienced a median PFS of 11.8 months (HR, 0.26; 95% CI, 0.18-0.38; P < .001), he says. The hazard ratio, a key statistical indicator, underscored the notable efficacy of cilta-cel observed in this clinical trial, according to Usmani. However, it's important to note that the anticipated adverse effects of cytokine release syndrome and infection were noted in patients receiving cilta-cel, Usmani says. Despite these treatment challenges, the overall data painted an impressive picture of the therapy's efficacy, Usmani states.

Further analysis delved into prespecified subgroups, particularly focusing on high-risk patients and those with a heavier disease burden. Encouragingly, these analyses revealed that even in these difficult-to-treat patient populations, treatment with the CAR T-cell therapy conferred notable benefits over SOC regimens, Usmani says. This finding is particularly significant as it indicates that interventions such as CAR T-cell therapy may hold the most promise for patients facing the greatest challenges in their disease management, Usmani concludes.