Evaluation and management of chimeric antigen receptor (CAR) T-cell-associated neurotoxicity

Adoptive cell therapies are a group of cancer immunotherapies that involve the infusion of engineered immune cells targeting specific tumor antigens, with chimeric antigen receptor (CAR) T cells at the vanguard of this revolution in cancer therapy. Several CAR T-cell products have been approved for the treatment of leukemia and lymphoma and many more are currently undergoing evaluation in clinical trials for the treatment of other liquid and solid malignancies. Despite their remarkable effectiveness, as with other immunotherapies, CAR T cells are frequently associated with systemic and neurologic toxicity. There has been a major effort by many institutions to develop specific protocols to guide the management of treatment-associated toxicities (eg, cytokine release syndrome [CRS]). However, neurotoxic effects of CART-cell therapies are more difficult to evaluate and treat, not easily lending themselves to an algorithmic approach to diagnosis and management. Given the steadily expanding use of CART-cell therapies for various malignancies, it is of critical importance for neuro-oncologists to be familiar with the clinical presentation and management principles of CAR T-cell-associated neurotoxicity. Here, we present key principles for the evaluation and management of patients affected by CART-cell-associated neurotoxicity based on the most recent evidence.

Automated summary

CAR T-cell therapies are a promising approach in cancer immunotherapy, although systemic and neurologic toxicity remain major concerns; specific protocols for managing treatment-associated toxicities, particularly neurotoxic effects, are still being developed; neuro-oncologists must be familiar with the clinical presentation and management principles of CAR T-cell-associated neurotoxicity as the use of CART-cell therapies continues to expand.