Early Steroid Use May Mitigate Adverse Effects Associated With Axicabtagene Ciloleucel CAR-T Therapy

Early steroid use could help mitigate toxic cytokine release syndrome (CRS) and neurologic events associated with chimeric antigen receptor T-cell (CAR-T) therapy according to the findings of a nonrandomized safety expansion of the ZUMA-1 multicenter, single-arm registrational phase 1/2 study. The study results were presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, held in Orlando, Florida.

In the ZUMA-1 study, patients with relapsed/refractory large B cell lymphoma treated with more than 2 prior systemic therapies were treated with axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 CAR-T therapy. However, 11% of patients experienced CRS and 32% of patients experienced neurologic events. In an effort to increase safety, researchers added a cohort to evaluate the effect of earlier steroid use on preventing CAR-T associated CRS and neurologic events. Patients in this new cohort received steroid intervention if grade I neurologic events and/or grade 1 CRS with no improvement after 3 days of supportive care was observed.

The new cohort that received earlier steroid treatment had fewer incidences of CRS (2%) and neurologic events (17%) than the previous cohort with late or no steroid treatment. The overall response rate to treatment was comparable between the 2 cohorts, 73% vs. 51%, respectively. There were also no differences in CAR T-cell expansion between the 2 cohorts (59 cells/uL in the early steroid group vs 42 cells/uL in previous cohort). Lastly, the cohort that received earlier steroid treatment had lower levels of key biomarkers indicative of severe neurologic events.

Overall earlier steroid use appears to reduce the incidence of CAR-T associated CRS and neurologic events. However, the study authors caution, “Conclusions are limited by the nonrandomized study design, differences in population sizes, and in baseline characteristics between cohorts. Optimizing [adverse events] management is important to improve the benefit-risk profile of CAR-T cell therapy.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.

Reference

Topp M, Van Meerten T, Houot R, et al. Earlier steroid use with axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B cell lymphoma. Oral presentation at: 61st ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 243.