Comparison of venetoclax and ivosidenib/enasidenib for unfit newly diagnosed patients with acute myeloid leukemia and IDH1/2 mutation: a network meta-analysis

Because of lacking of head-to-head comparison between venetoclax and IDH1/IDH2 inhibitors (ivosidenib/enasidenib) for newly diagnosed unfit patients with acute myeloid leukemia (AML), the optimal option for these patients still remains undefined. We searched relevant published reports. Three RCTs with 180 IDH1 mutant and 165 IDH2 mutant patients were identified. Indirect comparison of OS using fixed effects network meta-analysis (NMA) models indicated venetoclax plus azacitidine (Ven-Aza) significantly improved survival than enasidenib plus azacitidine (Ena-Aza) (HR:0.30, p = 0.005) for those newly diagnosed patients with AML and IDH2 Mutation. And, for those IDH2 mutation patients, Ven-Aza also had the highest probability of 98.3% (OS analysis) and 84.0% (CR/CRi analysis) to be the best intervention among these first-line treatment regimens (Ven-Aza, Ena-Aza and Aza). And, there was a favorable trend towards Ven-Aza in survival analysis (HR:0.69, p = 0.42), when compared to ivosidenib plus azacitidine (Ivo-Aza) for those newly diagnosed patients with AML and IDH1 Mutation. For those IDH1 Mutation, venetoclax plus azacitidine (Ven-Aza) had the highest probability of 65.8% (OS analysis) and 73.0% (CR/CRi analysis) to be the best intervention among these first-line treatment regimens (Ven-Aza, ivosidenib plus azacitidine (Ivo-Aza) and azacitidine (Aza)). In conclusion, venetoclax plus azacitidine could be a good option for unfit newly diagnosed patients with acute myeloid leukemia and IDH1/2 mutation. Considering our limits (only trial data-based network meta-analysis et al.), future trials directly comparing these regimens are warranted.