Therapeutic trade-offs between ide-cel and cilta-cel in RRMM: A meta-analytic comparison of efficacy and adverse events

Abstract Background: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells in the bone marrow. For patients with relapsed or refractory multiple myeloma (RRMM), chimeric antigen receptor (CAR) T-cell therapies targeting B-cell maturation antigen (BCMA), including idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel), have shown promising efficacy. However, challenges remain regarding durability of response, toxicity profiles, and optimal therapeutic choice. Methods: A meta-analysis was conducted to compare treatment responses and adverse events (AEs) associated with Ide-cel and Cilta-cel in patients with relapsed/refractory multiple myeloma (RRMM). Comprehensive searches were performed in PubMed, Scopus, and Embase through May 2025. Eligible studies reported outcomes for either or both CAR-T therapies. Data was extracted on key AEs including cytokine release syndrome (CRS), hematologic toxicities (e.g., cytopenias), neurotoxicity (ICANS), and infections, as well as treatment response categories (e.g., Overall Response Rate (ORR), Very Good Partial Response (VPGR), Stringent Complete Response (SCR), Partial Response (PR), and Complete Response/Complete Response with Recovery (CR/CRR)). A random-effects meta-analysis using inverse-variance weighting was used to estimate pooled odds ratios (ORs), proportions, 95% confidence intervals (CIs), and p-values. Outcomes reported in fewer than three studies were excluded from interpretation. Results: Out of 23 studies identified, 20 met inclusion criteria and were included in the meta-analysis. A total of 3,217 patients were included, with 1,726 receiving Ide-cel and 1,491 receiving Cilta-cel. Regarding treatment response, significant differences were observed in two categories. The ORR was significantly lower with Ide-cel compared to Cilta-cel, with a pooled odds ratio (OR) of 0.31 (95% CI: 0.11–0.87, p = 0.026), indicating that patients treated with Cilta-cel had over three times greater odds of achieving an overall response. In the analysis of AEs, CRS occurred more frequently with Ide-cel, showing a statistically significant difference compared to Cilta-cel. Grade 3/4 thrombocytopenia was also significantly more frequent with Ide-cel, . Other hematologic toxicities, including neutropenia, lymphopenia, anemia, and leukopenia, did not differ significantly between the two treatments. The meta-analysis results offer a comprehensive overview of all treatment response categories and adverse events Conclusion: This meta-analysis highlights key distinctions in both efficacy and safety between Ide-cel and Cilta-cel in patients with relapsed/refractory multiple myeloma. Cilta-cel was associated with a significantly higher overall response rate, while Ide-cel showed greater odds of achieving VGPR. However, Ide-cel also showed a higher risk of CRS and severe thrombocytopenia. These findings suggest that while both therapies offer clinical benefit, their differing profiles may support a tailored approach to therapy selection, aligning treatment choice with patient-specific factors such as disease burden, comorbidities, and tolerance to potential toxicities.