Tucidinostat plus pediatric-inspired chemotherapy for newly diagnosed adult ETP-ALL/LBL: a single-arm, phase 2 trial.

Early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a distinct subtype of T-ALL/LBL, characterized by a poor response to initial chemotherapy, a high relapse rate, and an inferior outcome. The treatment options for ETP-ALL/LBL are currently limited, and there are no reported clinical trials available for ETP-ALL/LBL. From June 2018 to June 2022, we conducted a single-arm, single-center, phase 2 trial (NCT03553238) in newly diagnosed ETP-ALL/LBL (age 14-55). Patients (N = 54) received pediatric-inspired chemotherapy plus tucidinostat, which was orally administered once daily at a dosage of 10 mg from induction 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. 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%), and infection (53%). Tucidinostat 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.