Chimeric Antigen Receptor T-cell Therapies in Lymphoma Patients with Central Nervous System Involvement

Background and objective:
CAR T-cell therapy has significantly improved the outcomes of patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). However, most clinical trials excluded patients with central nervous system (CNS) involvement due to uncertain efficacy and safety.


Material and methods:
On January 1, 2022, we searched PubMed to identify all published literature associated with current commercial CAR T-cell therapies for B-NHL, including tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi- cel), brexucabtagene autoleucel (brexu-cel), and lisocabtagene maraleucel (liso-cel). Studies that involved patients with either primary or secondary CNS lymphoma, and evaluated response rate, adverse events (AEs), or survival were included and summarized.


Result:
Herein, we summarize the results of 11 studies qualified for our inclusion criteria, reporting 58 lymphoma patients with CNS Involvement with 44 evaluable for clinical response, 25 for immune effector cell-associated neurotoxicity syndrome (ICANS) and 48 for Cytokine release syndrome (CRS). Objective response was achieved in 62% (16/26) of patients, and CR was achieved in 52% (23/44) of patients. Forty-four percent (11/25) developed ICANS, and 35% (17/48) developed severe ICANS (grade≥3). CRS was reported in 63% (15/24) of patients, while severe CRS (grade>3) was reported in 7% (3/42) of patients.


Conclusion:
Based on our PubMed literature review, we conclude that CAR T-cell therapy may benefit patients with CNS lymphoma with promising response rates and acceptable AE. However, definite conclusions cannot be drawn until data with a larger sample size is available.