Fever Characteristics and Impact on Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy

Fever is a common adverse effect of CAR T-cell therapy, but the impact of fever on safety and efficacy are not well understood. The study sought to the impact of fever and its characteristics on safety and efficacy post CAR T-cell therapy. A total of 40 patients were included. While early-onset and higher magnitude fever do not appear to affect safety or efficacy of CAR T, absence of fever may reduce efficacy.Background: Fever is a hallmark symptom of cytokine release syndrome (CRS) after chimeric antigen receptor (CAR) T -cell therapy. Fever characteristics and the impact of fever on safety and efficacy post CAR T are not well understood. We sought to explore the impact of fever and its characteristics on safety and efficacy post CAR T-cell therapy. Patients and Methods: We reviewed 40 patients with various hematologic malignancies (non-Hodgkin lymphoma, acute lymphoblas-tic leukemia, multiple myeloma) treated with CAR T-cell therapy between March 2019 and March 2022. We evaluated all patients who developed fever after CAR T infusion and analyzed the association of fever with toxicity (CRS and neuro-toxicity) and efficacy (overall response (ORR) and complete response (CR) at day + 90 post CAR T infusion). Fever was defined as per Lee cr iter ia (equal to or greater than 38 degrees C). CRS and immune-effector cell associated neurotoxic-ity syndrome (ICANS) were graded using American Society for Transplantation and Cellular Therapy grading system. Results: Fever occurred in 75% (30/40) of patients. Rates of all grade and grade 3 + CRS and ICANS were 75%, 2%, 33% and 10%, respectively. Fever occurred within 24 and 72 hours after CAR T infusion in 40% and 53% of patients, respectively. Fifty percent of patients received tocilizumab (toci) for CRS. After the first dose of toci, fever recurred in 38% of the patients, of which 67% had recurrence within 24 hours. Day + 90 CR rates were 43% and 10% in patients with and without fever, respectively (Table 3). Conclusion: While fever is common after CAR T-cell therapy, early-onset and higher magnitude do not appear to affect safety or efficacy of CAR T. Absence of fever may affect response to CAR T.