Comparative Effectiveness of Ciltacabtagene Autoleucel in CARTITUDE-4 Versus Real-World Physician’s Choice of Therapy from the Flatiron Registry in Lenalidomide-Refractory Multiple Myeloma

Ciltacabtagene autoleucel (cilta-cel) is approved for relapsed or refractory multiple myeloma (RRMM). In the CARTITUDE-4 study (NCT04181827), cilta-cel demonstrated superior efficacy versus pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone in patients with RRMM after 1-3 prior lines of therapy (LOT). We conducted an indirect treatment comparison to understand the comparative efficacy of cilta-cel versus real-world (RW) physician's choice of treatment for lenalidomide-refractory MM. De-identified data from the Flatiron Health MM cohort registry (January 2020 to May 2024) were compared with data from CARTITUDE-4 (data cutoff May 1, 2024). Key eligibility criteria for CARTITUDE-4 were used to match patients from the Flatiron database. Baseline covariates of prognostic significance were adjusted using inverse probability of treatment weighting. Outcomes for comparative effectiveness included progression-free survival (PFS), RW PFS, time to next treatment (TTNT), and overall survival (OS). Sensitivity analyses were conducted. The CARTITUDE-4 cohort included data from 208 patients who received cilta-cel; the median follow-up was 33.6 months. The real-world cohort included 932 patients (1445 eligible LOT) from the Flatiron database; the median follow-up was 23.6 months. In base case analyses, compared with the Flatiron cohort, patients treated with cilta-cel had improved PFS (hazard ratio HR 0.29 95% confidence interval (CI) 0.22-0.36; p < 0.001), RW-PFS (HR 0.29 95% CI 0.23-0.37; p < 0.001), TTNT (HR 0.32 95% CI 0.25-0.41; p < 0.001), and OS (HR 0.59 95% CI 0.41-0.84; p = 0.003). These findings were consistent across all sensitivity analyses. Cilta-cel lengthened TTNT and demonstrated meaningful prolongation in PFS and OS compared with real-world physician's choice for lenalidomide-refractory MM. These data highlight the value of cilta-cel as an effective therapy in earlier-line patients with relapsed, lenalidomide-refractory MM exposed to proteasome inhibitors and immunomodulatory drugs. CARTITUDE-4: ClinicalTrials.gov ID NCT04181827.