Adv Ther. 2025 Jul 4. doi: 10.1007/s12325-025-03278-5. Online ahead of print.
ABSTRACT
INTRODUCTION: The phase 3 CARTITUDE-4 trial demonstrated superiority of ciltacabtagene autoleucel (cilta-cel) over daratumumab, pomalidomide and dexamethasone, or pomalidomide, bortezomib and dexamethasone, in lenalidomide-refractory patients with relapsed/refractory multiple myeloma (RRMM) who received 1-3 prior lines of therapy. The comparative efficacy of cilta-cel was previously evaluated against other common regimens. Here, we present an updated comparative efficacy assessment, including OS, between cilta-cel (CARTITUDE-4 34-month median follow-up) and common regimens.
METHODS: Individual patient data were available from CARTITUDE-4 (cilta-cel), CASTOR (daratumumab, bortezomib and dexamethasone [DVd]), CANDOR (daratumumab, carfilzomib and dexamethasone [DKd] and carfilzomib and dexamethasone [Kd]) and APOLLO (pomalidomide and dexamethasone [Pd]). Inverse probability of treatment weighting (IPTW) was used to adjust for key baseline patient characteristic imbalances. Relative efficacies were estimated with response rate ratios and 95% confidence intervals (CIs) for response rates, with hazard ratios (HRs) and 95% CIs for PFS and OS. Sensitivity analyses using alternative statistical approaches were explored.
RESULTS: After excluding 53 patients with prior anti-CD38 therapy exposure, cilta-cel (n = 155) was compared with DVd (n = 44), DKd (n = 98), Kd (n = 46) and Pd (n = 92). Baseline covariates were generally well balanced across cohorts after IPTW. Cilta-cel showed significant improvements in PFS (HR 0.21-0.58; p ≤ 0.01) and OS (HR 0.31-0.55; p < 0.05) vs all regimens. With longer follow-up, the relative benefit of cilta-cel versus other regimens further increased on deeper levels of response. Although all results, except ORR, significantly favored cilta-cel, the DKd comparison provided the most conservative estimates.
CONCLUSION: This updated analysis confirms previously observed significant superiority of PFS and response outcomes of cilta-cel while showing significant OS benefit compared with common regimens for this population. These findings support cilta-cel as an effective treatment for lenalidomide-refractory RRMM patients as early as second line.
TRIAL REGISTRATION: CARTITUDE-4 ClinicalTrials.gov ID: NCT04181827.
PMID:40613875 | DOI:10.1007/s12325-025-03278-5
