Risk of Infection: Real-World Analysis of (Ide-cel) Idecabtagene Vicleucel and (Cilta-cel) Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma

Purpose/Objective: Anti-BCMA (B-cell maturation antigen) CAR T-cell therapy has emerged as a promising treatment for relapsed/refractory multiple myeloma (RRMM). BCMA is highly expressed on malignant plasma cells, making it an ideal target for CAR T-cell therapy. However, this innovative approach comes with unique challenges, including potential immunosuppression, hypogammaglobulinemia, and susceptibility to infections due to on-target off-tumor B-cell depletion. In this study, we compared the incidence and types of infections following Idecabtagene Vicleucel (Ide-cel) and Ciltacabtagene Autoleucel (Cilta-cel) CAR T-cell therapies in a real-world setting.

Methods: We utilized the Trinetx database to investigate the risk of infection following anti-BCMA CAR T-cell therapy using Ide-cel and Cilta-cel. Our methodology involved creating two distinct cohorts: the Ide-cel group (439 patients) and the Cilta-cel group (173 patients). We specifically focused on infections occurring after anti-BCMA CAR T-cell therapies. To address potential confounding, we conducted propensity score matching based on baseline characteristics, resulting in 75 matched patients per cohort. Our analytical approach included measures of association, number of instances, and Kaplan-Meier survival estimates. Additionally, we employed T-test statistics to assess differences in infection rates between the Ide-cel and Cilta-cel groups.

Results: The risk of infection was analyzed between the Ide-cel and Cilta-cel cohorts. Infections occurred in 33.6% of patients in the Ide-cel group and 30.8% in the Cilta-cel group, including bacterial, viral, and fungal infections (Risk difference 0.028, CI -0.108, 0.164, p=0.69). The 3-year survival probability was 40.7% for the Ide-cel group and 42.7% for the Cilta-cel group, with no significant difference between the groups (Log-rank test p=0.433). Intestinal infectious diseases, viral infections, and fungal infections were observed in 8% vs 6.3%, 21.6% vs 19.4%, and 8.8% vs 8.7% of the Ide-cel and Cilta-cel groups, respectively, with no statistically significant differences. A numerical difference was noted in bacterial infections (17.5% vs 11.2% for Ide-cel vs Cilta-cel), but it was not statistically significant (Risk difference 0.063, CI -0.007, 0.134, p=0.103). However, a statistically significant difference was found in Pneumocystis Jirovecii pneumonia (PJP) infections (2.3% vs 5.7%, Risk difference -0.034, CI -0.071, 0.003, p=0.032) between the Ide-cel and Cilta-cel cohorts.

Conclusion: Our findings emphasize the importance of vigilant infection monitoring and management during anti-BCMA CAR T-cell therapy. This study highlights the value of real-world data in understanding the safety profiles of Ide-cel and Cilta-cel in RRMM treatment, specifically regarding infection risk. Clinicians must balance therapeutic efficacy with the potential for infectious complications. Importantly, our data reveal a similar comparative infection risk between the two cohorts, suggesting that either CAR T-cell product can be considered. Although the infection risk is comparable between the two groups, it still leads to significant complications in the post-CAR T-cell therapy setting. Therefore, further research is crucial to develop better preventive and management strategies, ultimately improving patient outcomes in this evolving therapeutic landscape.