Phase II Study on Venetoclax (Ven) Plus Decitabine (Dec) (Ven-Dec) for Elderly (≥60 <75years) Patients with Newly Diagnosed High-Intermediate Risk Acute Myeloid Leukemia (AML) Elegible for Allogeneic Stem Cell Transplantation: Final Report of Ven DEC GITMO Study

Background Allogeneic stem cell transplantation (allo-SCT) is widely regarded as the most effective consolidation treatment for patients with intermediate to high-risk ELN AML. However, despite its potential curative benefits, many elderly patients (aged ≥60) are unable to undergo this procedure due to comorbidities and/or inability to tolerate intensive chemotherapy and achieve a complete remission (CR). As a result, only a small proportion of these patients are able to benefit from allo-SCT. Aims The VEN-DEC GITMO trial is a prospective, multicenter, single arm, phase II study designed to assess the safety and efficacy of a “chemo-free” combination of Venetoclax and Decitabine (VEN-DEC) as a bridge to allo-SCT in elderly patients (60-75y) with intermediate to high-risk ELN AML. The primary endpoint of the study was the percentage of patients who underwent transplant in first CR. The study aimed to enroll 100 patients, with a projected dropout rate of 12%. The study was considered successful if 14 or more patients underwent transplant in CR. Methods Venetoclax (up to 400mg oral daily) plus decitabine (20 mg/m2 for 5 days every 28 days) were administered for 2 cycles. Patients who achieved complete remission (CR), defined according to ELN criteria as CR/CRi/MLFS, were required to undergo allo-SCT within 2 months. Patients who did not respond (NR) or achieved partial remission (PR) after C2 could receive an additional 2 cycles of the therapy, in order to achieve a CR prior to transplant. Patients who did not respond or achieved only a PR were discontinued from the study and could be treated according to the policies of their respective Centers. Results Overall, 100 patients were enrolled by 25 Italian GITMO transplant Centers as of December 2022. The data cut-off was on July 17th, 2023. Table 1 provides details on the cohort's characteristics. Notably, more than 50% of patients presented with myelodysplasia-related changes and/or therapy-related AML, and 47% of cases had an abnormal karyotype. Seven patients (7%) were excluded due to screening failure. The remaining 93 patients started the 1 st cycle of treatment, and 78 patients completed the 2 nd cycle of VEN-DEC and were evaluable for treatment response. Overall, 58 patients achieved complete remission (CR/CRi/MLFS) after 2 cycles (74%), while partial or non-response occurred in 20 cases. Four out of 20 (20%) PR/NR patients at C2 achieved CR after two additional cycles of therapy for a total of 62/93 (67