Managing CAR T-Cell Toxicity: Impact of Steroid Prophylaxis on Toxicity and Outcomes
Authors: Upadhyay Laxmi , Shan Ul Abedin Muhammad , Yu Stephen , Thompson Jesse , Hinshaw Tyler , Gropp Jarom , Al-Saeed Nawaf , Cumpstom Aaron , Veltri Lauren , Safi Salah Ud Din 
Published: December 2024

Introduction: Chimeric antigen receptor (CAR) T-cell therapy has shown promising effects in treating relapsed/refractory hematological malignancies, significantly improving outcomes. However, CAR T-cell therapy is associated with side effects like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The incidence of CRS ranges from 41% to 94%, and ICANS from 21% to 64%, with grade 3 or higher CRS ranging from 1% to 24%. Prophylactic use of steroids has shown promising results in decreasing the incidence of CRS and ICANS in the ZUMA-1 cohort 6, including only axicabtagene ciloleucel (axi-cel) patients. Our study aimed to assess the effects of prophylactic steroids on the incidence of CRS, ICANS, and treatment outcomes post-CAR T-cell therapy with different CAR T-cell products.

Methods: An IRB-approved, single-institution retrospective chart review was conducted for CAR T-cell therapy patients at West Virginia University Hospital between January 2018 and January 2024. Patient demographics and other data were collected from the electronic medical record (EMR), recorded in Redcap, and analyzed using R statistics. Prophylactic 10 mg dexamethasone was given to the patient at the provider's discretion for three days, starting on day 0 to day +2 of CAR T-cell therapy infusion. Statistical analysis was performed using Fisher's exact, t-test, and Chi-squared tests.

Results: The study included 54 CAR T-cell patients, with a mean age of 63 ± 13, comprising 67% male and 33% female, 100% non-Hispanic, 98% white, follicular lymphoma 9%, DLBCL 58%, multiple myeloma 30%, and ALL 4%. Of the study population, 35% (19) patients received prophylactic steroids (steroid group), and 65% (35) did not receive prophylactic steroids (non-steroid group). In the steroid group, 37% received lisocabtagene maraleucel (liso-cel), 37% axi-cel, and 26% idecabtagene vicleucel (ide-cel). In the non-steroid group, 31% received ide-cel, 31% axi-cel, 17% liso-cel, 11% tisagenlecleucel, and 9% brexucabtagene autoleucel. The overall incidence of CRS was 67% (36/54), with 42% (8/19) in the steroid group and 80% (28/35) in the non-steroid group (p=0.01). The steroid group had 75% grade 1 CRS and 25% grade 2 CRS, with no grade 3 or 4 CRS. The non-steroid group had 64% grade 1, 29% grade 2, and 7% grade 4 CRS. Common CRS symptoms in the steroid group were fever (42%), while in the non-steroid group, symptoms included fever (77%), hypotension (17%), hypoxia (6%), and multiorgan failure (6%). The overall incidence of ICANS was 44%, with 32% in the steroid prophylaxis group and 51% in the non-steroid group (p=0.26).

First 30-day infection risk in the prophylactic steroid group was 53% (10/19) compared to a non-steroid group of 34% (12/35); p = 0.39, but the post-30-day infection was significantly lower, 32% vs. 63% in the steroid group compared to the non-steroid group (p = 0.05). The disease outcomes at 30 days for the prophylactic steroid group vs. non-steroid group were complete remission (CR) (42% vs. 29%), partial remission (PR) (29% vs. 43%), progression (32% vs. 9%), and death (0% vs. 9%), with p = 0.09. The disease outcomes at six months for the prophylactic steroid group vs. non-steroid group were CR (47% vs. 29%), PR (16% vs. 23%), progression (0% vs. 9%), relapse (0% vs 11%), and death (37% vs. 23%) with p = 0.32.

Conclusion: This study found that patients receiving prophylactic steroids in various CAR T-cell therapy products had a statistically significant reduction in the incidence of CRS, with no grade 3 or 4 CRS diagnosis. There was also a significantly lower rate of infection after 30 days. The steroid group also had a lower incidence of ICANS, although this did not reach statistical significance. The treatment outcomes showed no effects on the efficacy of the products. There was no 30-day mortality in the steroid group. Overall, prophylactic steroids reduced CRS without affecting the efficacy of the products. Further prospective studies are needed to assess the effects of prophylactic steroids on these individual products.