Chimeric antigen receptor T-cell therapy and immune effector cell-associated neurotoxicity syndrome: A meta-analysis

Chimeric antigen receptor (CAR) T-cell therapy, a form of adoptive immunotherapy, has expanded treatment options for various hematologic malignancies. However, CAR T therapy is associated with a range of side effects, including immune effector cell-associated neurotoxicity syndrome (ICANS), with variable incidence and severity.

To evaluate the incidence and characteristics of ICANS following CAR T therapy in different hematological diseases, with a focus on product-specific variations.

We searched PubMed, Embase, and Cochrane Library through 2/16/2024. Pooled incidence and 95 % confidence intervals (CIs) for ICANS (overall, more severe, and less severe) were estimated via a random-effects model. Separate meta-analyses were conducted for each lymphoma type - large B-cell lymphoma (LBCL), multiple myeloma (MM), and mantle cell lymphoma (MCL).

Of 259 articles reviewed, 30 studies were meta-analyzed. Among LBCL patients, the incidence of ICANS appeared lower with tisagenlecleucel (16.5 %, 95 % CI: 12.9-20.9; n = 1108 patients) than with axicabtagene ciloleucel (45.6 %, 95 % CI: 39.6-51.7; n = 1579). In MM patients, the incidence appeared lower with ciltacabtagene autoleucel (10.4 %, 95 % CI: 5.2-19.9; n = 348) than with idecabtagene vicleucel (18.3 %; 95 % CI: 15.4-21.5; n = 631). For MCL patients (n = 198), brexucabtagene autoleucel showed a high overall incidence of ICANS (61.2 %; 95 % CI: 54.2-67.8), with more severe events (32.9 %; 95 % CI: 26.7 %-39.7 %) slightly exceeding less severe ones (28.6 %; 95 % CI: 22.7 %-35.3 %).

Tisa-cel and cilta-cel showed a more favorable ICANS safety profile in LBCL and MM patients, respectively, while brexu-cel showed a higher ICANS incidence in MCL patients. Further comparative studies are needed to adjust for treatment-related confounders.