Venetoclax Combined with Three-Day Multi-Frequency Decitabine and Homoharringtonine (DEC3-VEN-HHT) As Induction Therapy in Newly Diagnosed Core-Binding Factor Acute Myeloid Leukemia

Background: The core-binding factor acute myeloid leukemia (CBF-AML) is a distinct subtype of acute myeloid leukemia (AML), typically associated with a favorable prognosis. The complete response (CR) rate of conventional induction chemotherapy is around 60%-80%, but it is consistently associated with significant myelosuppression and substantial medical costs. In recent years, more small molecule targeted drugs had been used in the treatment of AML, especially venetoclax combined with demethylation drugs. Our preliminary research had shown that venetoclax （VEN）combined with three-day multi-frequency decitabine (DEC) can markedly enhance improve CR rate. To further explore the induction regimen, we have designed a protocol Ven combined with three-day multi-frequency DEC and Homoharringtonine (HHT) as aninduction therapy in AML with RUNX1/RUNX1T1 or CBFβ/MYH11. Objective: To evaluate the efficacy and safety of Ven combined with three-day multi-frequency DEC and HHT in de novo AML patients with RUNX1/RUNX1T1 or CBFβ/MYH11. Methods A single-arm prospective clinical trial conducted in China Inter-Province Group of Blood Diseases (CPGBD). Twenty-two patients with the newly diagnosed CBF-AML were enrolled since January 2024, median age 62-years old (range 17-73). The induction regimen includes VEN administered at 100 mg on day 1, 200 mg on day 2, and 400 mg from days 3 to 14; DEC is administered at 20 mg/m² every 8 hours from days 4 to 6 (infusion time >2 hours); HHT is administered at 2.0mg/m2 /day days 4 to 8. If patient oral triazole, the dose of VEN decreased to 100mg/day. After achieving complete remission (CR), the patients received consolidation (including Medium or high dose Ara-c) and maintenance therapy. Allo-HSCT depends on patient efficacy. The primary endpoint is the overall response rate (ORR) after one cycle of induction therapy, which includes complete remission (CR), complete remission with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), and partial remission (PR). Results: By June 30, 2024, 22 patients had been enrolled in the study,with a median age of 62-years old (range 17-73), 63.5% (14/22) being male and 68.2% (15/22) diagnosed AML with RUNX1/RUNX1T1. All patients received induction chemotherapy. The cCR(CR+CRi) rate after one cycle of induction was 95.45%(21/22, 95% CI, 87%-100%), with the CR rate was 90.1% (20/22). One NR patient achieved CR after salvage treatment. Subgroup analysis showed that cCR(CR+CRi) rate was 93.33%(14/15, 95% CI, 80%-100%) in AML with RUNX1/RUNX1T1 and 100% in AML with CBFβ/MYH11. Among those who achieved cCR, the MRD negativity rate was 86.36% (95% CI, 72%-100%) by flow cytometry and fusion gene quantification 1.29% (0-12.45%) by PCR. Grade 3 to 4 anemia, thrombocytopenia, and neutropenia were the most frequent hematological adverse events during the induction treatment and occurred in all patients. The most frequent grades 3-4 nonhematological adverse events were febrile neutropenia. No patients died during induction. Conclusions: Ven combined with three-day multi-frequency DEC and HHT is a highly effective and safe induction therapy for de novo AML patients with RUNX1/RUNX1T1 or CBFβ/MYH11.