Dr Lin on Cilta-Cel in Lenalidomide-Refractory Multiple Myeloma

"It is another validation that reaching MRD status and sustained mid-status continue to translate into better outcomes in this new modality of treatment."

Yi Lin, MD, PhD, hematologist/oncologist, Division of Hematology, chair, Cellular Therapeutics Cross-Disciplinary Group, Mayo Clinic, discusses findings from the phase 3 CARTITUDE-4 trial (NCT04181827), which evaluated ciltacabtagene autoleucel (cilta-cel; Carvykti) vs standard of care (SOC) in patients with lenalidomide (Revlimid)-refractory multiple myeloma, focusing on minimal residual disease (MRD) negativity as a treatment outcome.

Updated findings from the study presented at the 2024 ASH Annual Meeting revealed that cilta-cel generated an MRD-negativity rate of 89% vs 38% for SOC at a 10⁻⁵ threshold (P < .001). At a 10⁻⁶ threshold, these rates were 86% and 19%, respectively (P < .001). Additionally, MRD negativity with cilta-cel occurred rapidly, with most patients reaching this status within two months of infusion. Subgroup analyses demonstrated a consistent MRD benefit across all prespecified patient populations, reinforcing the depth and durability of response with cilta-cel.

Prior data from CARTITUDE-4 supported the April 2024 FDA approval of cilta-cel for the treatment of adult patients with relapsed or 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.

These findings have a practical impact on patient management, Lin notes explaining that MRD assessment provides an early indication of response, allowing clinicians to monitor patients with reduced clinical burden. Unlike conventional continuous therapies, cilta-cel enables a treatment-free interval following a single infusion, offering patients the opportunity for less frequent clinic visits and extended follow-up intervals.

This transition can be challenging for patients accustomed to ongoing therapy, but MRD negativity serves as a reassuring indicator of disease control, informing clinical decisions regarding surveillance and ongoing management, she says.

These data suggest may further supporting the earlier integration of cilta-cel into treatment strategies, she says. Lin concludes that the robust MRD responses observed in CARTITUDE-4 validate cilta-cel as a preferred approach over SOC, particularly for patients seeking deep remission and reduced treatment burden.