Increased Rate of Anemia and Discontinuation in Older Patients with Myelofibrosis Treated with Ruxolitinib

<b>Background/Objectives</b>: Myelofibrosis (MF) predominantly affects older individuals, and its incidence increases with age. Ruxolitinib (RUX), a JAK1/2 inhibitor, effectively reduces spleen volume and relieves disease-related symptoms in MF patients and can be prescribed regardless of age. Although advanced age is associated with poorer MF prognosis, the influence of patient age on RUX treatment efficacy and safety has not been fully elucidated. <b>Methods</b>: In this single-center, retrospective study, we included 216 adult MF patients who initiated RUX therapy between 2012 and 2024. Patients were stratified by age at the start of RUX as follows: <65 (<i>n</i> = 105), 65-74 (<i>n</i> = 64), and ≥75 years (<i>n</i> = 47). Clinical data were analyzed in order to assess the impact of age on RUX-associated responses, toxicities, and survival. <b>Results</b>: Compared to younger patients, those ≥65 years showed features of more advanced MF and 45% higher odds of not achieving SR [OR = 1.45 (95% CI, 1.10-1.91), <i>p</i> = 0.009]. Patients ≥65 years presented a higher incidence of drug-related anemia at 3 (<i>p</i> = 0.003) and 6 months (<i>p</i> = 0.020). These patients had a two-fold increased risk of RUX discontinuation [HR = 2.07 (95% CI, 1.30-3.31) (<i>p</i> = 0.002) and presented a shorter OS than younger patients [HR = 2.74 (95% CI, 1.67-4.49)] (<i>p</i> < 0.001). In the sub-analysis focused on patients older than 65 years, very elderly patients (≥75 years) exhibited similar baseline characteristics, SR rates, median RUX treatment duration (<i>p</i> = 0.22), and OS (<i>p</i> = 0.86) to the 65-74 years cohort. More patients in the very elderly group presented an infectious event grade ≥ 2 (19.2%) than in the 65-74 years group (3.1%) (<i>p</i> = 0.008). <b>Conclusions</b>: RUX demonstrates overall robust rates of SR and favorable OS across all age groups. However, patients aged ≥65 years experienced higher rates of adverse events and worse outcomes. Our data support RUX usage in all age cohorts while highlighting the need for tailored strategies and close clinical monitoring in older patients.