ArticleJournal for immunotherapy of cancer2026
Comparative clinical outcomes and single-cell profiling of CD19 CAR-T versus blinatumomab for relapsed/refractory B-ALL.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCD19-targeting chimeric antigen receptor T-cells (CAR-T) and blinatumomab represent two leading immunotherapies for relapsed/refractory B cell acute lymphoblastic leukemia (r/r B-ALL). Despite sharing the same target, their differential clinical efficacy and underlying mechanisms remain unclear.
methodsThis retrospective study enrolled 106 r/r B-ALL patients (61 CD19 CAR-T vs 45 blinatumomab) between February 2020 and August 2023. The complete response (CR) rate, long-term survival, and therapeutic toxicities were compared between the two cohorts. Additionally, we conducted scRNA-seq on nine samples of patient-derived CAR-T/ blinatumomab-elicited T cells after infusion and performed a head-to-head comparison in vitro.
resultsOverall, the CR or CR with incomplete count recovery (CR/CRi) rate by day 28 after infusion was 96.6% (56/58) in the CAR-T cohort and 77.8% (35/45) 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. In patients with higher tumor burden (minimal residual disease >20%), CAR-T was associated with a longer LFS (HR 0.453, 95% CI 0.226 to 0.908, p=0.026) compared with blinatumomab. In patients with relapsed disease, CAR-T showed prolonged LFS (HR 0.415, 95% CI 0.221 to 0.778, p=0.006) and a trend toward improved OS (p=0.088). All toxicities were reversible, and any adverse events (AEs) were similar (98.4% vs 88.9%), but severe AEs (grade ≥3) were higher with CAR-T, especially cytokine release syndrome (42.6% vs 13.3%, p<0.001). In addition, scRNA-seq data 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 is consistent with the possibility that CAR-T cells may sustain effector function and cytotoxicity following tumor engagement, whereas blinatumomab-elicited T cells tended to show relatively higher exhaustion and reduced cell recovery.
conclusionsOur 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, despite a higher severe toxicity profile.
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