Optimization of the Clinical Journey of Unfit Patients With Newly Diagnosed Idh1m Acute Myeloid Leukemia

The management of acute myeloid leukemia (AML) in elderly or unfit patients has undergone a paradigm shift with the integration of molecular diagnostics and targeted therapies. Among actionable alterations, IDH1 mutations define a biologically distinct subgroup for which ivosidenib combined with azacitidine has recently emerged as a standard of care. However, initial clinical management remains complex. Three main themes emerged from the expert panel’s discussion: all patients should be tested for IDH1m, with turnaround time of 3-5 days; adequate patient monitoring during treatment is essential to detect the earliest signs of differentiation syndrome and QTc prolongation; appropriate management of concomitant therapies is required, not only for azole derivatives administered for antifungal prophylaxis, where need. This paper provides a comprehensive and evidence-based framework for optimizing early management in unfit patients with newly diagnosed IDH1-mutated AML, integrating data from randomized trials, real-world studies, and updated evidence on antifungal prophylaxis and drug–drug interactions in the era of targeted therapies.