CAR T
Published on March 11, 2025
Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL
by Alex Kadhim
A multicenter retrospective study published in Blood Advances, has investigated the impact of prior inotuzumab ozogamicin (InO) treatment on outcomes after brexucabtagene autoleucel (brexu-cel) therapy in adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). The study analyzed data from 189 patients who received brexu-cel, comparing those previously treated with InO to InO-naïve patients. While response rates and toxicity profiles were similar between groups, InO-exposed patients exhibited inferior progression-free survival (PFS) and overall survival (OS) in unadjusted analyses. However, after adjusting for disease and patient characteristics, prior InO exposure did not significantly impact PFS, suggesting that poor outcomes were more likely due to underlying aggressive disease rather than a direct effect of InO on CAR T-cell efficacy.
The rationale for the study stems from conflicting reports on whether InO exposure influences the effectiveness of CAR T-cell therapy. InO and Brex-cel share similar indications, and InO is often used as a bridging therapy before CAR-T administration. Some studies suggest that InO may impair CAR-T expansion due to B-cell depletion, while others indicate no significant impact. The researchers aimed to clarify this relationship by using real-world data from the ROCCA multicenter cohort, analyzing patient responses, survival outcomes, and potential confounders like disease burden and pre-treatment history.
The findings showed that InO-exposed patients had significantly worse survival outcomes in unadjusted models, but this association disappeared in multivariate analysis, indicating that disease biology rather than InO itself was the primary determinant of prognosis. Notably, InO non-responders had particularly poor outcomes after brexu-cel, reinforcing the idea that treatment resistance to InO reflects an aggressive disease phenotype that remains refractory to CAR-T therapy. The study concluded that InO should not necessarily be avoided before brexu-cel, but patients with prior InO exposure may require additional post-CAR consolidation strategies to improve long-term outcomes.
Reference
Aldoss I, Roloff GW, Faramand R, et al. Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL. Blood Adv. 2024;8(23):6139-6147.
http://doi.org/10.1182/bloodadvances.2024013747
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