A venetoclax-cytarabine-based induction regimen incorporating a translation inhibitor for adult patients with de novo acute myeloid leukemia.

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.