Comparative Outcomes and Molecular Response Predictors of IDH1/2-Mutated Adult Acute Myeloid Leukemia (AML) Patients (Pts) after Frontline Treatment with Intensive Induction Chemotherapy (IC), Targeted Inhibitors, or Hypomethylating Agents (HMA) (Alliance)

Background: The identification of mutations in IDH1 and IDH2 in ~20% of AML pts has ushered in the modern era of precision medicine in AML. The functional implications of the resulting neomorphic activity of these mutated enzymes, has resulted in FDA-approved targeted therapies. Similarly, the changes in methylation due to IDH mutations (IDHm) have shown high responses with HMA-based regimens. In the frontline setting, where traditional IC regimens are also used, no clear guidance exists which choice elicits the best outcomes for IDHm pts. Furthermore, emerging data on the importance of the biologic context on the response to different agents, including co-existing gene mutations and pt age, pose additional questions that need to be systematically addressed in order to determine the best-individualized approach. We set out to address this question, and provide data-driven treatment decision support for the ~20% of AML pts harboring IDHm.