Dr Sallman on the Rationale For Investigating Fedratinib in MDS/MPN Overlap Syndromes

David A. Sallman, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, discusses the rationale for conducting a phase 2, multi-institutional, investigator-initiated clinical trial (NCT05177211) on the use of fedratinib (Inrebic) in patients with myelodysplastic syndromes (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes and chronic neutrophilic leukemia.

This investigator-initiated trial was primarily motivated by the challenging treatment paradigm for patients with MDS/MPN overlap syndromes, Sallman begins. The unique characteristics of this patient population contribute to the exclusion of these patients from most MDS and MPN trials, he states. Despite the heterogeneity within this patient population, patients often have similar symptoms, Sallman note. These patients also often experience symptomatic splenomegaly and significant symptom burdens akin to those associated with MPNs, Sallman explains.

The central objective of the trial was to assess the potential applicability of JAK inhibitors, which have transformed the treatment paradigm for primary myelofibrosis, to patients with MDS/MPN overlap syndromes, he expands. Given the limited therapeutic options available for these patients, the trial explored the off-label use of the FDA-approved dose of fedratinib in this population, Sallman elucidates. Eligible patients were those with symptomatic splenomegaly, quantified through imaging, or those with substantial symptom burdens assessed through baseline and sequential symptom scores, he says.

The study incorporated standard methodologies, including serial lab counts, imaging of the spleen, sequential assessment of symptomatic question scores, and bone marrow biopsies, to gauge efficacy, Sallman continues. Presented as an oral presentation at the 2023 ASH Annual Meeting, the trial demonstrated that patients with MDS/MPN overlap syndromes who received fedratinib experienced response rates comparable with those of patients with symptomatic primary myelofibrosis, according to Sallman. Notably, patients exhibited both symptom and spleen responses, and these responses have proven to be durable thus far, he says. These findings indicate the potential effectiveness of using JAK inhibitors, specifically fedratinib, to address the therapeutic challenges faced by patients with MDS/MPN overlap syndromes, Sallman concludes.