Sustained Full-Dose Ruxolitinib Shows Manageable Toxicity Among Patients With MF
Key Takeaways:
- Among 24 patients with myelofibrosis (MF), treatment with full-dose ruxolitinib was associated with significant reductions in spleen length.
- Increased doses did not lead to an increase in infection, with toxicities remaining manageable and the incidence of second malignancies and mortality low.
- These findings suggest the long-term feasibility of maximizing ruxolitinib dosing in select patients with MF.
Since its approval by the US Food and Drug Administration (FDA) 10 years ago, ruxolitinib has become the standard frontline treatment for MF. Although multiple studies have documented its clinical efficacy, little research has evaluated the impact of sustained exposure to maximum doses.
Researchers conducted a real-world study to assess the long-term feasibility and safety of dose-intensified ruxolitinib among consecutive patients with MF.
Study Methods and Outcomes
The study included 24 patients who received the maximum approved dose of ruxolitinib (25 mg twice daily) at least once between 2015 and 2025. Median follow-up from treatment initiation was 60.9 months.
Patients were assigned to 1 of 3 categories based on dose intensity: high intensity, intermediate intensity, and minimal intensity. The high-intensity group contained 11 patients, 6 were in the intermediate group, and 7 made up the minimal group.
Impact of Full-Dose Ruxolitinib
Spleen response was observed in 21 patients, with 3 being excluded due to lack of assessment. Among the 21 analyzed, the median change from baseline was –16.5%, with 17 patients experiencing a reduction in spleen length. Only 1 patient had a reduction of 35% or greater.
Across the cohorts, spleen reduction occurred in 7 patients in the high-intensity group, 5 patients in the intermediate-intensity group, and 5 patients in the minimal-intensity group.
Sustained exposure to maximum doses of ruxolitinib was not associated with an increased risk of infection or mortality. Hematologic toxicities were manageable and did not lead to treatment discontinuation.
Four patients died during the study: 1 from COVID-related complications, 1 from advanced pulmonary malignancy and cardiorespiratory failure (with a history of cardiovascular complications), and 2 from advanced disease and multiple comorbidities. Second malignancies occurred in 3 patients: non-melanoma skin cancer, cervical tumor, and colorectal carcinoma.
Implications for Managed Care
This study illustrated an association between prolonged exposure to full-dose ruxolitinib and spleen reduction among select patients with MF. Infections and complications did not increase with dosage, indicating a manageable safety profile.
The findings suggest that dose intensity may be a crucial part of treatment strategy that can provide clinical benefits without increasing toxicity.
The authors concluded that “these findings should not be extrapolated indiscriminately to all patients with myelofibrosis, but rather viewed as representative of outcomes achievable in carefully selected patients managed in experienced centers.”
Reference
Mendicino F, Caridà G, Bruzzese A, et al. High-dose ruxolitinib (25 mg twice daily) in myelofibrosis: feasibility, safety, and long-term treatment exposure in a real-world cohort. Ann Hematol. 2026;105:284. doi:10.1007/s00277-026-07020-1
