Cytokine Release Syndrome after Chimeric Antigen Receptor Transduced T-Cell Therapy in Cancers: A Systematic Review

Patients with refractory or relapsed malignant disorders are in desperate condition, with few therapeutic options left, if any. Chimeric antigen receptor (CAR) transduced T-cell transplantation is a novel approach that has shown promising results as well as serious adverse events. This study aimed to systematically review the current data on the cytokine release syndrome (CRS) as a major side effect of CAR therapy. A systematic literature review was conducted to find reports of CAR T-cell therapy in the context of cancer patients and to extract reports of severe CRS. The factors that could significantly affect the incidence of CRS were investigated. Mortality rates were also compared regarding the occurrence of CRS. The incidence of severe CRS was 9.4% (95% confidence interval: 8.3-10.5) in the reviewed studies. Younger and older patients (vs. adults), higher doses of CAR T-cell infusions, lymphodepletion (LD) before CAR T-cell infusions, specific LD regimens, the source of allogeneic cells for the construction of CAR, chronic lymphocytic leukemia as the tumor type (vs. lymphoma), and CD28 as costimulatory domain in the structure of CAR were significantly associated with CRS events. Patients experiencing severe CRS had a significantly higher mortality rate within 2 and 3 months after transplantation. In conclusion, this study found many factors that could predict severe CRS and future clinical trials could reveal the relevance of appropriate interventions to the incidence and outcomes of CRS in cancer patients undergoing CAR T-cell transduced infusions.