Efficacy and Safety in Patients with Lenalidomide-Refractory Multiple Myeloma and 1–3 Prior Lines Who Received a Single Infusion of Ciltacabtagene Autoleucel As Study Treatment in the Phase 3 Cartitude-4 Trial

Introduction CARTITUDE-4 (NCT04181827) is a phase 3 trial comparing ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen chimeric antigen receptor-T cell (CAR-T) therapy, with standard of care (SOC; pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]) in patients (pts) with lenalidomide (len)-refractory multiple myeloma (MM). Pts in the cilta-cel arm had significantly improved progression-free survival (PFS), higher rates of ≥complete response (CR), and higher overall response rate (ORR) versus SOC in the intent-to-treat (ITT) set. Objective We report efficacy and safety in pts receiving cilta-cel (‘as-treated’ set) in the experimental arm. Methods Pts had 1 to 3 prior lines of therapy (LOT), with a proteasome inhibitor and immunomodulatory drug. A single cilta-cel infusion (target dose, 0.75 × 106 CAR+ viable T cells/kg) was administered after apheresis, bridging therapy (DPd [28-day cycles] or PVd [21-day cycles]), and lymphodepletion. Treatment responses and disease progression were assessed per IMWG criteria and minimal residual disease (MRD) negativity at 10−5 by next-generation sequencing. Endpoints were analyzed with the Kaplan-Meier method. Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity (ICANS) were graded per ASTCT criteria with other adverse events (AEs) graded per NCI-CTCAE criteria. Results As of November 1, 2022, 176 of 208 pts received cilta-cel (median age, 61 years; 34%,1 prior LOT; 6%, ISS stage III; 60%, high-risk cytogenetics; 17%, soft-tissue plasmacytoma; 13%, high tumor burden; 11%, triple-class refractory). Baseline characteristics were consistent with the ITT set. In the as-treated set, median follow-up was 16 months (mo); the majority of pts received bridging therapy resulting in effective disease control prior to cilta-cel. Median PFS and duration of response were not reached. From infusion, 12-mo PFS rate was 85%; 12-mo overall survival rate was 92%. Of 176 pts, 175 responded (99% ORR); 86% achieved ≥CR. Median time to first response was 2.1 mo; more pts achieved ≥CR over time (Figure A). Of 144 MRD-evaluable pts, 111 (77%) achieved MRD negativity and ≥CR and had improved PFS versus pts who remained MRD positive and/or had 更多