Cardiovascular adverse events in patients with cancer treated with chimeric antigen receptor (CAR) T-cell therapy: A meta-analysis of both controlled and single-arm clinical trials.

e19006 Background: Chimeric antigen receptor (CAR-T) Chimeric antigen receptor (CAR) T-cell therapy presents a promising avenue in the treatment of hematological malignancies. However, the application of CAR-T cell therapy comes with a range of adverse effects, some of which are not fully understood yet. While previous research has primarily focused on immune effector cell-associated neurotoxicity (ICANs) and cytokine release syndrome (CRS), the cardiovascular safety profile of CAR-T cell therapy remains less defined. This meta-analysis assesses the incidence of cardiovascular (CV) events associated with CAR-T therapy, thereby providing critical insights into these events and guiding clinical decision-making. Methods: We conducted a Pubmed search of clinical trials evaluating the effect of CAR-T cell therapy in cancer patients with cardiovascular adverse events. For phase III trials, a quantitative assessment of Grade 3 or higher CV events was performed using the Review Manager (Rev-Man) Version 5.4 (The Cochrane Collaboration, 2020) and the results were reported as Odd Ratio (OR) with 95% Confidence Interval (CI). A fixed effect model was used. For phase I/II trials, the event rates were calculated for all-grade as well as grade 3 and higher CV adverse events. Results: A total of four Phase III clinical trials with 1345 patients were included for the comparison analysis. Among those trials, two involved multiple myeloma patients, and two involved large B cell lymphoma patients. The age range across trials was 20-83 years with a male-to-female ratio of 1.5:1. The analysis revealed that there was no statistically significant difference in Grade 3 or higher CV events between the CAR-T cell therapy and control (standard of care) groups: OR with 95% CI was 1.44 (0.73,2.82) (p=0.29). Grade 3 and above CV adverse event rates were 3.4% for the CAR-T and 2.1% for the control groups. Notably, there were two CV deaths in the CAR-T group and one CV death in the control group. Additionally, a total of 41 single-arm, Phase I/II clinical trials with 1479 participants were analyzed. Seven studies included solid cancers such as metastatic pancreatic cancer, biliary tract cancer and melanoma. The age range was 17-86 yr and male/female ratio was 1.5:1. Total all-grade CV adverse event rate was 21.83% and total grade 3 and above CV adverse event rate was 8.82%. There were eight CV deaths. Conclusions: There were significantly more CV adverse events reported in Phase I/II trials when compared to those reported in Phase III trials. This indicates that CV adverse events are important consequences of CAR-T cell therapy but are likely underreported in the Phase III clinical trials. Increased awareness and more standardized evaluation of CV adverse events of CAR-T is needed in the future clinical trials.