Hagop Kantarjian, MD, University of Texas MD Anderson Cancer Center, Houston, TX, discusses a Phase II clinical trial (NCT03586609) of venetoclax in combination with cladribine plus low dose cytarabine (CLAD/LDAC), alternating with azacitidine (aza), in older acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. Previous studies have shown that CLAD/LDAC produces deep responses in combination with azacitidine, establishing it as an effective triple nucleoside analogue regimen. Additionally, venetoclax can improve remission rates and survival outcomes when combined with hypomethylating agents (HMA) such as aza, compared to HMA monotherapy. Thus, adding venetoclax to CLAD/LDAC and azacitidine therapy was trialed in AML, with an aim to further improve response rates in unfit or older patients. The results showed this regimen to be well tolerated and highly effective in the older cohort, warranting further study. Given the proven benefits of additional venetoclax, it was added to an established intensive induction regimen of cladribine, cytarabine and idarubicin in a trial (NCT02115295) of younger AML patients, which resulted in high rates of lasting MRD-negativity and promising overall survival. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.