Management of Elderly and Frail Patients with Philadelphia-Negative Myeloproliferative Neoplasms—A Narrative Review

Philadelphia-negative myeloproliferative neoplasms (MPNs) predominantly affect older adults, yet individuals over 65 years remain underrepresented in clinical trials, limiting evidence-based guidance for the most affected population. Aging can profoundly modify MPN biology through clonal hematopoiesis, chronic inflammation, vascular aging, and marrow senescence. This can amplify thrombotic risk, symptom burden, and treatment intolerance. These biological changes intersect with multimorbidity, frailty, and polypharmacy to create a distinct clinical phenotype that challenges traditional age-based treatment paradigms. This narrative review synthesizes current evidence on how aging influences therapeutic decision-making across ET, PV, and MF. In cytoreductive therapy, hydroxycarbamide remains the mainstay for older adults. Interferon-based therapies may offer disease-modifying benefits in appropriately selected older patients, although evidence regarding their comparative tolerability and safety in very elderly and frail populations remains limited. JAK inhibitors provide meaningful symptomatic and splenic benefit across age groups, though cytopenias, dose reductions, and treatment interruptions are more frequent in older patients due to diminished marrow reserve and competing comorbidities. Antithrombotic management requires careful balancing of heightened thrombotic risk against age-related bleeding hazards, particularly in the context of atrial fibrillation, renal impairment, and acquired von Willebrand syndrome. Polypharmacy further complicates care through drug–drug interactions and altered pharmacokinetics. Beyond disease modification, symptom burden—especially fatigue, pruritus, and functional decline—often dominates quality-of-life priorities for older adults. Integrating geriatric assessment, competing risks frameworks, and patient-centered outcomes is essential to delivering biologically informed, goal-aligned care. Overall, management of older adults with MPNs must transition to personalized strategies that reflect aging biology, functional reserve, and individual priorities.