CELL INTELLIGENCE · 肿瘤细胞治疗研究

BACKGROUND: Translation inhibitors have been shown to accelerate acute myeloid leukemia (AML) cell apoptosis and regulate Akt activity and the Bcl-2 family, suggesting their potential benefit when combined with venetoclax and cytarabine in de novo AML patients. METHODS: The authors conducted a multicenter, open-label, single-arm study to assess the efficacy and safety of a venetoclax-cytarabine-based induction regimen incorporating a clinically available translation inhibitor in adult patients newly diagnosed with AML in China. RESULTS: A total of 52 cases (median age, 48.5 years; range, 18-60) were treated, with poor risk in 27% (14 of 52) of patients. The overall response rate was 90% (95% CI, 79-97) after one cycle of the regimen with 46 patients in composite complete remission. With a median follow-up of 816 days (interquartile range, 418-1143), the estimated 1-year overall survival (OS) and event-free survival (EFS) were both 81% (95% CI, 71-92). After induction chemotherapy, patients experienced decreases in CD4 + naive, CD8 + naive, Th2, and CD19 + cells, along with increases in CD4 + TEM, Th1, natural killer cells, and a higher Th1/Th2 ratio in both peripheral blood and bone marrow (BM), whereas BM-specific changes included a decrease in CD8 + naive cells and lower IL-10 levels post-treatment. CONCLUSION: This venetoclax-cytarabine regimen incorporating a translation inhibitor demonstrated efficacy and was well-tolerated in young adult patients with de novo AML, achieving high complete remission rates and encouraging OS and EFS. The induced immune-cell and cytokine shifts provide deeper insights into integrating translational inhibition with BCL2-targeted therapies and warrant further investigation in randomized controlled trials. This trial was registered at ChiCTR.org.cn as ChiCTR2100048208.