ABSTRACT Patients with B-cell acute lymphoblastic leukemia (B-ALL) and high disease burden (DB; ≥5% marrow blasts and/or extramedullary disease) before lymphodepletion (LD) experience inferior survival and increased toxicity following CD19-directed chimeric antigen receptor T-cell (CAR T) therapy. Bridging therapy (BT) administered between leukapheresis (LA) and LD is frequently used to reduce DB, yet the impact of successful cytoreduction on CAR T outcomes remains unclear. We retrospectively reviewed 154 patients with B-ALL treated with CD19-directed CAR T therapy at City of Hope between 2014 and 2024 who underwent disease assessments both pre-LA and pre-LD. High DB pre-LA were classified as high-to-low (H-L) if cytoreduction was achieved prior to LD or high-to-high (H-H) if DB remained elevated. Outcomes included cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), leukemia-free survival (LFS), and overall survival (OS). Among 124 patients with high DB pre-LA, 117 received BT, and 23% (n=28) achieved cytoreduction. Two-year LFS was significantly improved in H-L versus H-H patients (56.3% vs. 34.8%, p=0.04) with similar rates of grade ≥3 CRS and ICANS. Among BT modalities, only tyrosine kinase inhibitor (TKI)-based therapy increased the odds of cytoreduction (OR=3.77, p=0.03), but no individual BT type was independently associated with improved survival. Successful cytoreduction prior to CAR T infusion, rather than BT type, was associated with superior LFS. Optimizing individualized BT strategies to achieve effective cytoreduction while minimizing treatment-related toxicity may further improve outcomes in high-DB B-ALL.
Murphy et al. (Mon,) studied this question.