Outcomes of patients treated with venetoclax plus azacitidine versus azacitidine alone stratified by advanced age and acute myeloid leukemia composite model.

Venetoclax plus azacitidine is recognized as standard of care for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). However, some patients may still not be treated with venetoclax combinations due to frailty concerns. We evaluated efficacy and safety of venetoclax plus azacitidine vs. placebo plus azacitidine in patients with newly diagnosed AML ineligible for IC from the phase 3 VIALE-A study (NCT02993523) and the phase 1b M14-358 study (NCT02203773), stratified by two methods to potentially assess frailty. The first method was age-based (75-79, 80-84, ≥85 years; n = 303 pooled from both studies) and the second was fitness-based using the AML composite model (AML-CM), a comorbidity-based model to estimate mortality risk (Group A, B, C; n = 380, from VIALE-A). Efficacy, including composite complete remission and overall survival, were improved with venetoclax plus azacitidine vs. placebo plus azacitidine across age and AML-CM groups. Safety was generally similar between age and AML-CM groups and no new safety signals were identified. Taken together, these data suggest that patients benefit from venetoclax plus azacitidine regardless of age or degree of frailty and the combination may be considered for patients with AML who may be deemed frail. Clinical trial information NCT02993523; NCT02203773.