Newly approved treatments have increased the options available for patients with acute myeloid leukemia (AML), but have also generated questions concerning the selection of the most appropriate therapy for a given individual (Tables 1 & 2). The trials leading to the approval of these therapies were based on limited genetic data (e.g., cytogenetics, FMS-like tyrosine kinase-3 FLT3 status) and clinical parameters (e.g., age, comorbidities, therapy, or secondary AML). Data concerning effectiveness or lack of efficacy of a drug or drug regimen in specific AML subgroups is often determined after drug approval. For example, venetoclax (VEN) + azacitidine (AZA) lower intensity therapy (LIT), which is approved for the treatment of patients with newly diagnosed AML deemed ineligible for intensive chemotherapy (IC) or aged >75 years, was found to have limited efficacy in patients with mutated TP53. Despite the regulatory approved indications for VEN‑based LIT, some older and younger patients can be selected for either LIT or IC. Furthermore, with the availability of maintenance therapy after IC16, several important questions have emerged regarding the role of IC in older patients. No published prospective studies have compared IC with LIT in “fit” patients with newly diagnosed AML to inform treatment choice. Two retrospective propensity score matched real‑world data analyses of outcomes in patients with newly diagnosed AML (irrespective of the genetic profile) who received induction with VEN + AZA or IC, indicated no difference in overall survival (OS). However, one study showed improved complete remission (CR) and/or allogeneic hematopoietic stem cell transplant (alloHCT) rates in favour of IC (60.9% vs. 44.2%, P = 0.006 and 18.1% vs. 8.0%, P = 0.012, respectively). Other single‑centre retrospective studies comparing VEN + AZA with IC have yielded conflicting results. None of these studies provided information concerning the use of oral AZA maintenance therapy. The studies did suggest that outcomes may be dependent on specific genetic abnormalities and/or clinical factors. Currently, several Phase 2 trials are comparing VEN + AZA with IC in adult patients with newly diagnosed AML (NCT04801797, NCT05904106, NCT05554406, NCT05554393). Here, two case scenarios will be discussed to highlight issues surrounding treatment choice: a) fit individuals who are ≥75 years with newly diagnosed European LeukemiaNet (ELN)-defined favourable-risk AML and b) IC eligible persons who are ≥18 years with newly diagnosed ELN‑defined poor-risk AML, who require alloHCT in first complete remission (CR1) with curative intent.
Karen Yee (Mon,) studied this question.