Venetoclax and Homoharringtonine-Based Therapy Exhibited a Striking Response in Refractory/Relapsed Early T-Cell Precursor Acute Lymphoblastic Leukemia

维奈托克和高三尖杉酯碱联合疗法在难治性/复发性早期T细胞前体急性淋巴细胞白血病中表现出显著疗效。

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Abstract

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of T-ALL. Once refractory or relapsed, it is associated with a poor prognosis, with a complete remission (CR) rate of 36%-46% following re-induction therapy. Previously, we reported a synergistic effect of venetoclax (VEN) and homoharringtonine (HHT) in ETP-ALL, which potentially elicits notable clinical responses. Herein, we investigated the efficacy and safety of the V-HAG regimen (VEN, HHT, cytarabine, and granulocyte colony-stimulating factor [G-CSF]) in patients with refractory/relapsed ETP-ALL through a prospective, multicenter, single-arm, open-label, phase 2 clinical trial. A total of 18 patients were enrolled, and 100% of these patients achieved CR or CR with incomplete hematological recovery (CRi) after 1 cycle of the V-HAG regimen as re-induction therapy. As a follow-up, both the relapse rate and mortality rate were 33.3%. The 1-year overall survival and relapse-free survival were 76.7% (95% confidence interval [CI]: 53.2%-100.0%) and 55.7% (95% CI: 28.8%-82.6%), respectively. The most common grade 3-4 adverse events were neutropenia (100%), anemia (88.9%), and thrombocytopenia (100%). Notably, the VEN- and HHT-based therapy, V-HAG regimen, exhibits an extremely high efficacy in the treatment of patients with refractory/relapsed ETP-ALL with good tolerance, and it provides a promising therapeutic strategy for improving their outcomes.

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