A Markov analysis of azacitidine and venetoclax versus induction chemotherapy for medically-fit patients with AML.

While induction chemotherapy (IC) is the standard of care in medically-fit patients with newly diagnosed acute myeloid leukemia (AML), limited retrospective data indicate that adverse risk patients may benefit from azacitidine and venetoclax (aza-ven). Our goal was to perform a Markov decision analysis to determine whether IC or aza-ven is the optimal induction regimen in this population. Using the TreeAge software, Markov models were created for adverse risk and intermediate risk cohorts. A systematic review of the literature informed the transition probabilities and utilities included in the analyses. Our primary outcome was quality adjusted life years (QALY) gained over five years following diagnosis. Overall, adverse risk patients treated with IC gained 1.4 QALY, compared to 2.0 QALY in patients treated with aza-ven. Adverse risk patients treated with IC and allogeneic stem cell transplant (AlloSCT), IC, aza-ven and AlloSCT, and aza-ven gained 2.1, 1.5, 3.0, and 1.9 QALY, respectively. Meanwhile, intermediate risk patients treated with IC gained 2.0 QALY, compared to 1.7 QALY in patients treated with aza-ven. Intermediate risk patients treated with IC and AlloSCT, IC, aza-ven and AlloSCT, and aza-ven gained 2.7, 2.3, 2.6, and 1.8 QALY, respectively. We have demonstrated that medically-fit patients with newly diagnosed adverse risk AML may benefit from treatment with aza-ven over IC, while IC remains the preferred approach for intermediate risk patients. Our work challenges the use of the European LeukemiaNet risk classification in patients treated with aza-ven and highlights the need for prospective investigation into aza-ven as induction therapy for medically-fit patients.