Brexu-Cel Incurs High Real-World Rates of ICANS, CRS in R/R B-ALL 

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) were very common in a real world setting among adults receiving the CD19-directed CAR-T-cell therapy brexucabtagene autoleucel (brexu-cel) for relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), according to results of a phase 2 cohort study presented at the ASH Annual Meeting 2023.

“Severe ICANS was more common with active disease,” reported lead study author Noam E. Kopmar, MD, of the University of Washington and Fred Hutchinson Cancer Center, in Seattle, Washington. “There is a trend towards the same with severe CRS. There was not an observation of onset of CAR-T specific toxicity, specifically CRS and ICANS, beyond Day +21 from cell infusion.”

Adults with B-ALL frequently relapse but CD19-directed CAR-T therapy has expanded the set of treatment options. The FDA approved brexu-cel CAR-T for the treatment of adults 18 years and older with R/R B-ALL in October 2021, based on ZUMA-3 trial outcomes (ClinicalTrials.gov Identifier: NCT02614066). US cancer centers subsequently created the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) consortium. It is not affiliated with any biopharmaceutical companies, Dr Kopmar noted.

A total of 152 evaluable adult patients treated with brexu-cel for R/R B-ALL since October 2021 with at least 3 months of follow-up were enrolled; 57% were male and 51% were non-Hispanic White. Nearly one-third (31%) had Philadelphia chromosome-positive (Ph+) disease. The median number of prior treatments was 4 (range, 1 to 12). Half (51%) had more than 5% blasts.

A total of 133 patients (88%) experienced CRS, ICANS, or both. Of the 152 patients, 125 (82%) experienced some grade of CRS, including 13 (9%) experiencing grade 3 or higher. ICANS of any grade occurred in 85 (56%) patients, including 48 (31%) experiencing grade 3 or higher.

Grade 3 and higher ICANS rates were comparable to those previously reported in the ZUMA-3 clinical trial, Dr Kopmar noted. ICANS rates were 60% and 56% for ZUMA-3 and the ROCCA cohort, respectively; 25% and 31% experienced grade 3 or higher ICANS. For CRS, overall rates were 89% in ZUMA-3 and 82% in the ROCCA cohort, and 24% and 9% for grade 3 or higher CRS. 

CRS and ICANS treatment varied, with 103 patients (68%) receiving tocilizumab, 94 (62%) receiving corticosteroids, 32 (21%) receiving anakinra, and 6 patients receiving other agents.

Grade 3 or higher ICANS was associated with active disease, defined as 5% or higher marrow blasts and/or extramedullary disease, at the time of apheresis (odds ratio, 2.63; 95% CI, 1.28-5.38; P =.008). 

“Although CRS-related early mortality was rare, grade 3 [or higher] CRS was associated with a higher risk of death” (hazard ratio, 2.38; 95% CI, 1.00-5.66; P =.05), Dr Kopmar said.

Nine (6%) patients died by Day +28 from infusion. These deaths are “typically multifactorial,” Dr Kopmar noted, involving CRS in 3 patients, ICANS in 3 patients, infection in 5, disease relapse or progression in 2, and HLH in 1 patient.

Disclosures: This study was supported by a National Heart, Lung, and Blood Institute (NHLBI) T32 training grant. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Kopmar NE, Gooley T, Roloff GW, et al. Toxicity profile of brexucabtagene autoleucel (brexu-cel; CD19-directed CAR-T-cell therapy) in adult patients (pts) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL): results from a multicenter real-world outcomes study. Presented at ASH 2023. San Diego, CA. December 9-12, 2023.  Abstract 522.