Clinical Summary:

• Design/Population: A multicenter, phase 2 study evaluated fedratinib in patients with myelodysplastic/myeloproliferative neoplasms or chronic neutrophilic leukemia with proliferative features, including splenomegaly with or without significant symptom burden.
• Key Outcomes: Fedratinib demonstrated clinical activity, with responses observed in nearly half of patients and meaningful spleen and symptom improvements in a subset. Responses appeared enriched among patients with CSF3R mutations, and median progression-free and overall survival were approximately 37 months. The safety profile was manageable, with gastrointestinal toxicities most common.
• Clinical Relevance: Fedratinib may provide a treatment option for patients with proliferative myelodysplastic/myeloproliferative neoplasms and chronic neutrophilic leukemia, particularly those with splenomegaly, symptom burden, or potentially CSF3R-mutated disease.

Results from a phase 2 study demonstrated that fedratinib showed promising clinical activity among patients with myelodysplastic and myeloproliferative neoplasms and chronic neutrophilic leukemia. 

These results were presented by Andrew Kuykendall, MD, Moffitt Cancer Center and Research Institute, Tampa, Florida, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

In this multicenter study, 25 patients with atypical chronic myeloid leukemia (n = 6), chronic neutrophilic leukemia (n = 5), unclassifiable myelodysplastic and myeloproliferative neoplasms (n = 8), or myelodysplastic and myeloproliferative neoplasms-ring sideroblasts and thrombocytosis (n = 6) received 400 mg of once daily fedratinib in 28-day cycles. The primary end point was 24-week overall response, defined as complete response, partial response, or clinical benefit. Key secondary end points included progression-free survival (PFS), overall survival (OS), and duration of response.

At analysis, 3 patients remained on study treatment, and the median duration of therapy was 7.4 months. At week 24, 44% of patients achieved a response, including spleen volume reduction of at least 35% in 30% of patients and symptom improvement of at least 50% in 47% of patients. Four patients achieved both spleen and symptom responses. Among patients with splenomegaly who received at least 24 weeks of therapy, spleen volume decreased by an average of 30%. Among patients with symptomatic disease, total symptom scores improved by an average of 41%. CSF3R mutations were enriched among patients achieving spleen responses.

Median PFS was 36.9 months, and median OS was 36.9 months. The median duration of response was 7.6 months. Median OS was 19.8 months in patients with atypical chronic myeloid leukemia, 36.9 months in patients with chronic neutrophilic leukemia, and not reached in patients with either unclassifiable or ring sideroblast and thrombocytosis myelodysplastic and myeloproliferative neoplasms. 

The overall safety profile was consistent with previous experience with fedratinib. Serious adverse events were reported in 52% of patients. Events considered possibly related to fedratinib included acute kidney injury, low thiamine, colitis, diarrhea, arthralgia, and edema. The most common gastrointestinal adverse events of any grade were nausea (52%), constipation (48%), diarrhea (44%), and vomiting (16%).

“[Fedratinib’s] unique kinase inhibition profile may provide a mechanism for enhanced effectiveness in this pt population,” concluded Dr Kuykendall. 

Source:

Kuykendall AT, Jain T, Singh A, et al. A phase 2 study of fedratinib in patients with MDS/MPN and chronic neutrophilic leukemia. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 6509.