Retrospective study of CD19 CAR-T versus blinatumomab for relapsed or refractory B cell acute lymphoblastic leukemia

CD19-targeting CAR-T and blinatumomab are two leading immunotherapies for relapsd or refractory B cell acute lymphoblastic leukemia (R/R B-ALL). Their differential clinical efficacy is not clear. A retrospective study at Zhejiang University School of Medicine (Hangzhou, China) enrolled 106 R/R B-ALL patients who received CD19 CAR-T (n=61) or blinatumomab (n=45) between February 2020 and August 2023. Complete response with or without complete count recovery (CR/CRi) by day 28 after infusion was 96.6% in the CAR-T cohort and 77.8% in the blinatumomab cohort (p=0.008). With a median follow-up of 10 months (IQR 5.0-19.4), overall survival (OS) and leukemia-free survival (LFS) were comparable. Among patients with higher tumor burden (MRD > 20%), CAR-T was associated with longer LFS (HR 0.45; p=0.026) compared with blinatumomab. Among patients with relapsed disease, CAR-T showed prolonged LFS (HR 0.42; p=0.006) and a trend toward improved OS (p=0.088). All toxicities were reversible, and any adverse events (AEs) were similar, but grade ≥3 AEs were more frequent with CAR-T, especially cytokine release syndrome (42.6% versus 13.3%; p<0.001). Single-cell RNA sequencing provided correlative evidence of functional enrichment of effector cells in CAR-T samples during peak expansion at 2 weeks post infusion. Head-to-head comparison in vitro was consistent with the possibility that CAR-T cells may sustain effector function and cytotoxicity following tumor engagement, whereas blinatumomab-elicted T cells tended to show relatively higher exhaustion and reduced cell recovery. The authors conclude that these findings suggest that CD19 CAR-T therapy is associated with a higher CR/CRi rate compared with blinatumomab, particularly in patients with high tumor burden and relapsed disease, with a higher severe toxicity profile.