B05: RESULTS FROM A META-ANALYSIS OF CILTACABTAGENE AUTOLEUCEL COMPARED TO PHYSICIAN’S CHOICE OF TREATMENT IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA
Introduction: The CARTITUDE-1 trial (NCT03548207) is evaluating ciltacabtagene autoleucel (cilta-cel), a novel chimeric antigen receptor T-cell therapy, in patients with relapsed/refractory multiple myeloma (RRMM) who are triple-class exposed to immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody. Indirect treatment comparisons (ITCs) have been previously conducted between cilta-cel and physician’s choice of treatment (PCT) as no clear standard of care exists for patients with triple-class exposed RRMM and no direct head-to-head trials were performed to evaluate cilta-cel and other relevant treatments. Objective: To perform meta-analyses to derive single summary effect estimates for overall survival (OS) and progression-free survival (PFS) using pooled ITCs that evaluated cilta-cel versus PCT in patients with triple-class exposed RRMM. Methods: ITCs comparing the effectiveness of cilta-cel versus PCT on OS and PFS were included in this analysis. The data cut-off date for CARTITUDE-1 was February 2021, and data for PCT were based on the following sources: (i) Flatiron, a largely US community-based MM registry; (ii) long-term follow-up data from POLLUX (NCT02076009), CASTOR (NCT02136134), and EQUULEUS (NCT01998971), three global RRMM daratumumab randomized clinical trials; (iii) MAMMOTH, a retrospective study based in the US; and (iv) a representative German patient registry maintained by OncologyInformationService. The PCT group for each ITC comprised patients who fulfilled key eligibility criteria for the CARTITUDE-1 trial and was made comparable to CARTITUDE-1 using inverse probability of treatment weighting, resulting in ITCs that were appropriate for meta-analysis. The meta-analysis used a robust variance estimator to account for the use of CARTITUDE-1 in each pairwise ITC. The main meta-analyses included all patients treated with cilta-cel in CARTITUDE-1 compared with PCT. Sensitivity analyses considered ITC effect estimates based on all patients enrolled in CARTITUDE-1. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are reported for pooled summary effect estimates. Results: Based on available data, the main meta-analyses included four ITCs for OS and three ITCs for PFS. Significant improvement in OS (HR: 0.21, 95% CI: 0.13–0.34) and PFS (HR: 0.20, 95% CI: 0.07–0.63) was observed with cilta-cel versus PCT (Figure). Results of the main meta-analyses were confirmed with sensitivity analyses that included all enrolled patients. Conclusions: Cilta-cel demonstrated a significant OS and PFS advantage versus PCT in the meta-analyses, highlighting its potential as an effective treatment in patients with triple-class exposed RRMM.