Abstract
Background
Preclinical studies suggest that venetoclax and azacitidine have anti-leukemic activity in Philadelphia Chromosome-Positive acute lymphoblastic leukemia (Ph+ALL) and may synergize with TKIs. Accordingly, we performed a prospectively trial to investigate the efficacy and safety of the combination of venetoclax, azacitidine and flumatinib (VAF) in newly diagnosed adult patients with Ph+ALL.
Methods
Patients aged 18-65 years with a confirmed diagnosis of newly diagnosed Ph+ALL were eligible for inclusion in this investigator-initiated, single-center, single arm, phase 2 trail. The primary endpoint was complete molecular response (CMR) rate after two cycles of VAF. Secondary end points included adverse events (AEs), overall survival (OS), relapse-free survival (RFS), and cumulative incidence of relapse (CIR).
Results
Twenty patients were enrolled. 18 (94.7%) patients had major molecular response (MMR) or better after two cycles of VAF, and the CMR rate was 78.9%. Meanwhile, VAF was well tolerated with mild myelosuppression and rapid recovery of hemopoiesis. Common hematologic AEs ≥grade 3 were neutropenia (9 [45%]), thrombocytopenia (4 [20%]), anemia (3 [15%]) in cycle 1. The median time for thrombocytopenia, anaemia and neutropenia recovery were 2, 2.5 and 4 days, respectively. Patients received the second cycle of VAF in Day ward, except 2 (11%) were hospitalized for pneumonia and transfusion supports. With a median follow-up of 15.9 months (range 8.9-22.8 months), the estimated 2-year OS, RFS, and CIR were 88.7%, 77.5% and 22.5%, respectively.
Conclusion
The chemotherapy-free combination of venetoclax, azacitidine and flumatinib induced rapid and deep responses in newly diagnosed adult patients with Ph+ALL. In addition, VAF may also provide a Day-Clinic treatment modality for induction and early consolidation in Ph+ALL patients due to its well-tolerance.
Trial registration
ClinicalTrials.gov Identifier: NCT05433532.