Outcomes of Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma: A Systematic Review and Meta-Analysis

Introduction/Background/Significance: Ciltacabtagene autoleucel (cilta-cel) is a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy that has shown promising efficacy in patients with relapsed/refractory multiple myeloma (RRMM). To better assess the therapeutic outcomes and safety, we performed a meta-analysis of published clinical trials evaluating cilta-cel in this high-risk population.

Materials and Methods/Case Presentation/Objective: A systematic search of PubMed and clinicaltrials.gov was conducted to identify clinical trials reporting outcomes of cilta-cel in RRMM. Primary efficacy outcomes included overall response rate (ORR), complete response (CR) rate, and minimal residual disease (MRD) negativity. Safety outcomes included the incidence of grade 3/4 adverse events (AEs), cytokine release syndrome (CRS), neurotoxicity, and mortality. Meta-analyses were conducted using RevMan 5.3 with random-effects models. Pooled proportions and 95% confidence intervals (CIs) were calculated.

Results/Description/Main Outcome Measures: Four clinical trials comprising 589 patients were included. The pooled ORR was 90.2% (95% CI: 84.2–96.2; p < 0.001). The CR rate was 5.6% (95% CI: –2.1 to 13.2; p = 0.154). MRD negativity was achieved in 86.6% of patients (95% CI: 71.6–101.6; p < 0.001). Grade 3 or 4 AEs were reported in 78.5% of patients (95% CI: 52.9–104.1; p < 0.001), CRS occurred in 86.1% (95% CI: 74.5–97.7; p < 0.001), and neurotoxicity was reported in 14.4% (95% CI: 7.2–21.7; p < 0.001). The pooled all-cause mortality rate was 18.9% (95% CI: 15.8–22.1; p < 0.001).

Conclusions: Ciltacabtagene autoleucel demonstrates a high overall response rate and MRD negativity in RRMM, although the complete response rate remains modest. The therapy is associated with notable adverse effects, particularly CRS and neurotoxicity. These findings support cilta-cel's strong anti-myeloma activity but also demonstrate the need for proactive adverse effect management to preserve quality of life in treated patients. Given the heterogeneity and single-arm nature of the included studies, these results should be interpreted considering the variability across included trials. Further randomized and comparative trials are warranted to validate these findings.

References

1. Jian-Qing Mi et al. Phase II, Open-Label Study of Ciltacabtagene Autoleucel, an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor–T-Cell Therapy, in Chinese Patients With Relapsed/Refractory Multiple Myeloma (CARTIFAN-1). JCO 41, 1275-1284(2023).

DOI:10.1200/JCO.22.00690

2. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study

Berdeja, Jesus G et al.

The Lancet, Volume 398, Issue 10297, 314 - 324