Host Fitness: A Missing Dimension of Precision Medicine in Older Acute Myeloid Leukemia

ABSTRACT

The therapeutic landscape for older adults with acute myeloid leukemia (AML) has undergone a major paradigm shift with the advent of lower‐intensity targeted regimens, particularly hypomethylating agents combined with venetoclax. As treatment transitions from acute induction to prolonged, multi‐cycle administration, clinical success increasingly depends on the patient's capacity to sustain repeated cycles, manage cytopenias and infections, and maintain functional independence. Current precision oncology models excel at characterizing the leukemic clone via cytogenetics, genomics, and measurable residual disease (MRD); however, they provide limited insight into the patient's underlying biological reserve. In this perspective, we propose host fitness as a critical, complementary dimension of precision medicine in older AML. Host fitness is a dynamic, multidimensional construct encompassing functional reserve, body composition, nutritional status, immune competence, inflammatory burden, and metabolic resilience. Moving beyond traditional performance status and simplistic metrics like body mass index, longitudinal assessment of host fitness aims to identify actionable vulnerabilities, guide targeted supportive interventions, and optimize treatment persistence. Integrating continuous host‐fitness evaluation with clonal profiling establishes a dual host–tumor precision‐medicine framework designed to maximize therapeutic efficacy while preserving patient resilience and quality of life.