2025 Southeastern Residency Conference

Title: Real world analysis of safety and efficacy outcomes in lymphoma patients receiving CAR T-cell therapy with prophylactic dexamethasone

Authors: Alleah Al-Amery, Karin Abernathy, Darby Siler, Laura Beth Parsons, and Chelsea Mitchell

Background: Axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel) are CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies used to treat certain B-cell malignancies. Administration of CAR-T requires monitoring and management of potential adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Prior studies have demonstrated a reduced incidence of CRS and ICANS with prophylactic dexamethasone in axi-cel recipients without compromising efficacy. Though brexu-cel shares a similar structure to axi-cel, there are no studies assessing effect of corticosteroid prophylaxis in this population. This study seeks to bridge the gap in the literature and assess institutional practice regarding prophylactic dexamethasone in both axi-cel and brexu-cel recipients.

Methods: This was a retrospective study at a tertiary medical center, including patients who received axi-cel or brexu-cel for a lymphoma diagnosis between June 1, 2020 and July 31, 2024. Patients were excluded if they did not receive prophylactic dexamethasone on days 0, +1, and +2, were enrolled in a clinical trial, received CAR-T as an inpatient, were under 18 years old, or were treated on the pediatric oncology service. The primary endpoint was incidence of all-grade CRS and ICANS, compared to a historical control. Secondary endpoints included time to onset, severity, duration, and resolution of CRS and ICANS, as well as hospitalization rates, disease response at Day 30, and survival at Day 30.
 
Results: Of the 32 patients screened, 27 (axi-cel: N=17 ; brexu-cel: N=10) were included. Baseline demographics were similar between both axi-cel and brexu-cel groups and the respective historical controls. The axi-cel group had similar rates of CRS compared with historical controls that also received prophylactic dexamethasone (88% vs. 80%; p=0.70). Overall incidence of ICANS was lower (35% vs 53%, p=0.16) than historical comparator. Similarly, Grade 3+ ICANS was lower than comparator group (5.8% vs. 12.5%, p=1.00). The brexu-cel group had a lower rate of CRS compared with historical controls that did not receive prophylactic dexamethasone (80% vs. 91%, p=0.27). Though not statistically significant, the brexu-cel group had lower incidence of Grade 3+ CRS compared with historical controls (0% vs. 15% p = 0.60). Incidence of ICANS was similar across brexu-cel groups (60% vs. 63%, p=1.00). However, Grade 3+ ICANS was lower in the brexu-cel group compared with historical controls (10% vs. 31%, p=0.66). Median days to onset of CRS and ICANS were delayed with the addition of prophylactic dexamethasone prior to brexu-cel (CRS: 7 vs. 2, p =0.06; ICANS: 10 vs. 7, p=0.70).
 
Conclusion: This real-world assessment of prophylactic dexamethasone with axi-cel showed comparable results to the historical studies. Prophylactic corticosteroids with brexu-cel appears to decrease severity of both CRS and ICANS while also delaying onset. These results could increase feasibility of outpatient administration of brexu-cel. These results also mirror outcomes with dexamethasone prophylaxis with axi-cel.

Disclosure: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.