Dr Kuykendall on Fedratinib's Promising Efficacy in MDS/MPN Overlap Syndromes

Myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs) are clinically and molecularly complex diseases characterized by proliferative symptoms and aggressive clinical courses. Evaluation of mutational patterns and gene expression profiles suggests these diseases should be viewed as a spectrum rather than distinct entities, and treatment options remain limited and poorly defined, as patients are often excluded from clinical trials.

To address this unmet need, Andrew T. Kuykendall, MD, of Moffitt Cancer Center, led a phase 2, multi-institutional, investigator-initiated study (NCT05177211) evaluating fedratinib (Inrebic), a JAK2-selective kinase inhibitor, in patients with atypical chronic myeloid leukemia (aCML), chronic neutrophilic leukemia (CNL), MDS/MPN-unclassifiable, and MDS/MPN-ring sideroblasts and thrombocytosis per the 2016 WHO classification. Patients were required to have splenomegaly and/or significant disease-related symptoms, with overall response rate, defined as complete or partial response or clinical benefit, serving as the primary end point.

Fedratinib demonstrated promising clinical efficacy in MDS/MPN and CNL patients with proliferative features, and its safety profile was consistent with prior experience. Fedratinib's unique kinase inhibition profile may provide a mechanism for enhanced effectiveness in this patient population.

Kuykendall emphasizes that fedratinib is particularly well suited to this setting because it can target various proliferative pathways in MDS/MPN that other current standards of care may miss. His hope is that the data can support what is already being done in practice, potentially formalizing the use of fedratinib in a population that has historically lacked well-defined therapeutic options.

Results from this trial, presented at the 2026 ASCO Annual Meeting, represent an important step toward establishing evidence-based treatment strategies for patients with rare myeloid malignancies who carry a significant disease burden and limited alternatives.