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Real-World Comparison of Axicabtagene Ciloleucel and Lisocabtagene Maraleucel in Large B-Cell Lymphoma

In a multicenter retrospective study published in Blood Advances, authors from multiple institutions examined the impact of prior inotuzumab ozogamicin (InO) exposure on the outcomes of brexucabtagene autoleucel (brexu-cel) therapy in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). InO, an anti-CD22 antibody-drug conjugate, is commonly used in this setting, but its effect on subsequent CAR T-cell therapy outcomes has remained unclear. The study analyzed 189 patients treated with brexu-cel, comparing response rates, survival, and toxicity between those previously exposed to InO and those who were InO-naïve. While initial findings suggested that InO-exposed patients had inferior progression-free survival (PFS) and overall survival (OS), further analyses revealed that these differences were largely driven by underlying disease biology rather than a direct impact of InO on brexu-cel efficacy.

The authors sought to address growing concerns regarding whether prior InO exposure might impair the effectiveness of CAR T-cell therapy. Some earlier studies have reported conflicting findings on whether InO affects CAR T-cell expansion and persistence, potentially leading to reduced survival. Given the increasing use of InO as a bridge to transplantation or CAR T-cell therapy, clarifying its impact on brexu-cel outcomes is critical for optimizing patient selection and post-treatment strategies. The researchers assessed a range of clinical variables, including response to InO, leukemia burden, and post-CAR relapse patterns, to determine whether InO exposure was an independent risk factor for poorer outcomes.

While InO-exposed patients initially appeared to have worse survival outcomes, these differences were no longer significant after adjusting for other clinical factors. Notably, patients who failed to respond to InO had particularly poor outcomes with brexu-cel, suggesting that intrinsic disease resistance, rather than InO itself, drives survival differences. Thus, the study concluded that prior InO exposure should not necessarily preclude CAR T-cell therapy, but patients with refractory disease may require alternative treatment approaches or post-CAR consolidation strategies to improve long-term outcomes.

Reference

Aldoss I, Roloff GW, Advani AS, 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.

doi: 10.1182/bloodadvances.2024013747.