Toci or not toci: innovations in the diagnosis, prevention, and early management of cytokine release syndrome

Abstract

Cytokine release syndrome (CRS) remains a significant toxicity of chimeric antigen receptor T-cell (CAR-T) therapy for hematologic malignancies. While established guidelines exist for the management of Grade 2+ CRS with immunosuppressive agents such as tocilizumab or corticosteroids, the management of early-grade CRS (i.e. Grade 1 CRS with isolated fevers) has no such consensus beyond supportive care. In this review, we discuss early-grade CRS with an emphasis on its diagnosis, management, and prevention. Strategies to target early-grade CRS include immunosuppression preemptively (once CRS develops) or prophylactically (before CRS develops) as well as novel small-molecule inhibitors or fractionated CAR-T dosing. In the near future, next-generation CAR-T therapies may be able to target CRS precisely or obviate CRS entirely. If shown to prevent CRS-associated morbidity while maintaining therapeutic anti-neoplastic efficacy, these innovative strategies will enhance the safety of CAR-T therapy while also improving its operationalization and accessibility in the real-world setting.

Keywords:

• chimeric antigen receptor T-cell therapy
• cytokine release syndrome
• tocilizumab

Disclosure statement

Banerjee: Dr. Banerjee reports grants from Pack Health, personal fees from SparkCures, outside the submitted work. Shah: Dr. Shah reports personal fees from GSK, grants from Bluebird Bio, personal fees from Amgen, personal fees from Indapta Therapeutics, personal fees from Sanofi, grants and personal fees from BMS, personal fees from CareDx, personal fees from Kite, personal fees from Karyopharm, grants from Janssen, grants from Sutro Biopharma, grants from Teneobio, grants from Poseida, personal fees from Genentech, personal fees from Seattle Genetics, personal fees from Oncopeptides, personal fees from Surface Oncology, personal fees from Precision Biosciences, grants and personal fees from Nektar, outside the submitted work.