Comparison of regional differences in safety and efficacy of CAR-T therapy for hematologic malignancies in a real-world setting: a systematic review and meta-analysis

Background

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape of patients with hematologic malignancies. Nevertheless, geographic regions may lead to various outcomes, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), overall response rate (ORR), and complete response rate (CRR). However, the related evidence of real-world studies and systematic analysis remains limited.

Objective

This meta-analysis aims to compare the real-world incidence of CRS and ICANS, as well as therapeutic outcomes ORR/CRR, in patients with hematologic malignancy treated with CAR-T therapy across different regions.

Methods

A systematic literature search was conducted in Pubmed, Embase, and Cochrane Library databases published up to February 2025. Subgroup analyses were performed based on geographic regions and other factors.

Results

Seventy corhorts from 4 different regions comprising 9233 patients were included. North America exhibited the highest incidence of CRS at 83 %, surpassing Europe (82 %) and Asia (80 %) significantly (p < 0.01). However, no significant regional differences existed in grade ≥ 3 CRS. The incidence of ICANS was notably higher in North America (39 %) compared to Europe (32 %) and Asia (21 %; p = 0.08), with grade ≥ 3 ICANS also more prevalent in North America (16 %) than in Europe (9 %) and Asia (2 %; p < 0.01). Efficacy did not vary across different regions.

Conclusion

Patients in North America possessing elevated rates of CRS and grade ≥ 3 ICANS. The results provide valuable insights to the adverse effects when treating patients with CAR-T therapy across different regions in a real-world setting.