Andrew Kuykendall, MD, an assistant member at the H. Lee Moffitt Cancer Center of University of South Florida in Tampa, FL, discusses data from a phase 2 trial (NCT05177211) which evaluated fedratinib (Inrebic), a JAK2-selective kinase inhibitor, in patients with atypical chronic myeloid leukemia (aCML), chronic neutrophilic leukemia (CNL), myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN)-unclassifiable, and MDS/MPN-ring sideroblasts and thrombocytosis per the 2016 WHO classification.
According to findings from this multi-institutional, investigator-initiated study presented at the 2024 American Society of Hematology (ASH) Annual Meeting, fedratinib demonstrated promising efficacy and a manageable safety profile in this patient population.
At the time of data cutoff, 24 patients were enrolled and 19 patients were evaluable. A total of 53% of patients achieved a response at 24 weeks, including 50% symptom responses and 37.5% spleen responses. Of those treated for ≥24 weeks, spleen volume decreased by an average of 32%, and 85% showed symptomatic improvement. Responses were enriched in patients with CSF3R mutations (83%) and JAK-STAT pathway mutations (70%). Further, the median overall survival (OS) was estimated at 19.7 months.
“This was a very high-risk population, as these diagnoses are associated with poor prognosis. Despite that, we observed spleen responses in approximately 35% of patients, symptom responses in 50%, and some durable responses, with the median time on treatment nearing a year. These outcomes were particularly exciting given the molecular features of this patient population, which typically predict lower response rates,” Kuykendall shares.
Safety findings showed that fedratinib was well tolerated, The majority of adverse events (AEs) were grades 1 or 2, and the most commonly seen AEs were diarrhea (37.5%), constipation (37.5%), and anemia (29%). A single grade 4 neutropenia event resolved with dose adjustments.
“Regarding the safety profile, it was consistent with prior studies of fedratinib. There were some manageable low-grade gastrointestinal [adverse events]. We implemented a more proactive approach to mitigate these, including the use of antiemetics during the first 8 weeks. Overall, the [adverse event] profile remained manageable, and the efficacy outcomes likely exceeded our initial expectations,” adds Kuykendall.