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

Abstract

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.

Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies

“…The comparison between Tisa-cel versus Axi-cel in terms of toxicity or efficacy showed no differences in terms of severe CRS incidence but an increased incidence of ICANs in patients receiving Axi-cel products. This agrees with previous studies that have reported increased toxicity in patients infused with Axi-cel (37,46,47). However, no significant differences were observed in eventfree survival of patients infused with Tisa-cel or Axi-cel products.…”

CAR T-cell-associated neurotoxicity in central nervous system hematologic disease: Is it still a concern?

“…Among these, 25 were assessable for ICANS. They identified that 44% (11/25) developed ICANS, and 35% presented a severe form of the syndrome ( 88 ). Furthermore, Asghar et al reported collective data from 14 studies that comprised eight retrospective studies and six single-arm prospective studies/clinical trials, with a total of 137 patients.…”