From molecular biology to treatment: precision medicine in acute myeloid leukemia

De la biología molecular al tratamiento: medicina de precisión en leucemia mieloide aguda

Introduction: acute myeloid leukemia (AML) is a heterogeneous clonal neoplasm whose understanding has improved through molecular characterization, particularly with next-generation sequencing (NGS). These advances have enabled more accurate prognostic stratification, the use of measurable residual disease, and the development of targeted therapies, optimizing survival and treatment personalization, especially in older adults who are not candidates for intensive regimens.

Clinical case: a case of an 80-year-old functionally independent man (ECOG 0) diagnosed with AML with myelodysplastic changes and a normal karyotype after the incidental finding of pancytopenia. Treatment with azacitidine and venetoclax was initiated, achieving complete morphologic remission and good quality of life for 16 months, with dose adjustments due to myelosuppression. Upon relapse, an FLT3-ITD mutation was identified and gilteritinib monotherapy was started. Despite infectious complications and dose modifications, the patient showed a significant reduction in blasts, progressive hematologic recovery, and transfusion independence, remaining ambulatory and functional. AML in older adults requires an individualized approach integrating geriatric assessment and molecular characterization. Azacitidine–venetoclax is the standard of care for patients unfit for intensive induction, although limited by myelosuppression. At relapse, identification of actionable mutations such as FLT3 enables the use of selective inhibitors like gilteritinib, with a survival benefit over salvage chemotherapy.

Conclusion: this case highlights the clinical impact of precision medicine in older adults with AML by prolonging survival and preserving quality of life in a traditionally poor-prognosis population.