Background Early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a distinct subtype of T-ALL/LBL, with a dismal prognosis. The aim of this study was to investigate the effectiveness and safety of histone deacetylase inhibitor (HDACi) tucidinostat combined with pediatric-inspired chemotherapy for new diagnosed ETP-ALL/LBL.

MethodsThis phase 2 trial was conducted at Nanfang Hospital in China. Patients aged 14-55 years with newly diagnosed ETP-ALL/LBL were eligible. Patients received pediatric-inspired chemotherapy in combination with tucidinostat, which was orally administered once daily at a dosage of 10 mg from induction therapy to consolidation therapy. The primary endpoint was 3-year event-free survival (EFS). Secondary endpoints were overall survival (OS), relapse-free survival (RFS), complete remission rate and adverse events. This study is registered with ClinicalTrials.gov, number NCT03553238.

Findings From June 2018 to June 2022, 54 patients with ETP-ALL/LBL were enrolled (37 [68%] male; 17 [32%] female; 54 [100%] Asian; median age 24 years [IQR 19-31]). The composite complete remission (CRc, complete response [CR] plus complete response with incomplete blood count recovery [CRi]) rate and MRD negativity after induction therapy was 91% (49 of 54 patients) and 65% (35 of 54 patients), respectively. The MRD negativity after consolidation was achieved in 87% patients (47 of 54 patients). With a median follow-up of 39.3 months (IQR, 20.6 to 60.0), the 3-year EFS rate was 67.7% (95% CI 56.2-81.7), the 3-year OS rate was 71.5% (95% CI 60.2-84.9) and the 3-year RFS rate was 67.5% (95% CI 55.9-81.6). The most common grade 3-4 adverse events were neutropenia (94%), anemia (85%), thrombocytopenia (76%), infection (53%), and hypokalemia (21%).

InterpretationTucidinostat plus pediatric regimen is an effective and well-tolerated regimen for new diagnosed ETP-ALL/LBL, with high CRc and MRD negativity rates, as well as encouraging survival outcomes.

Disclosures

No relevant conflicts of interest to declare.

Off Label Disclosure:

TucidinostatÃ' is used as the initial treatment for newly diagnosed ETP-ALL/LBL.

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2024
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