Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications

Abstract

Chimeric Antigen Receptor T (CAR-T) cell therapy has dramatically changed prognosis and treatment of relapsed and refractory hematologic malignancies. Currently the 6 FDA approved products target various surface antigens. While CAR-T therapy achieves good response, life-threatening toxicities have been reported. Mechanistically, can be divided into two categories: (1) toxicities related to T-cell activation and release of high levels of cytokines: or (2) toxicities resulting from interaction between CAR and CAR targeted antigen expressed on non-malignant cells (i.e., on-target, off-tumor effects). Variations in conditioning therapies, co-stimulatory domains, CAR T-cell dose and anti-cytokine administration, pose a challenge in distinguishing cytokine mediated related toxicities from on-target, off-tumor toxicities. Timing, frequency, severity, as well as optimal management of CAR T-cell-related toxicities vary significantly between products and are likely to change as newer therapies become available. Currently the FDA approved CARs are targeted towards the B-cell malignancies however the future holds promise of expanding the target to solid tumor malignancies. Further highlighting the importance of early recognition and intervention for early and late onset CAR-T related toxicity. This contemporary review aims to describe presentation, grading and management of commonly encountered toxicities, short- and long-term complications, discuss preventive strategies and resource utilization.

Keywords

• chimeric antigen receptor T-cell therapy (CAR-T)
• adoptive immune cell therapy
• cytokine release syndrome
• late complications
• cytopenias
• hypogammaglobulinemia