A Phase 2 Study of Fedratinib in Patients with MDS/MPN and Chronic Neutrophilic Leukemia
At time of data cut-off, 10 pts have been enrolled with a median follow-up of 5 months. Eight pts remain on treatment. Baseline demographics, genetic makeup, and treatment history are shown in table 1. Enrolled pts include 1 with aCML, 4 with CNL, 4 with MDS/MPN-RS-T, and 1 with MDS/MPN-U. Three or more mutations were present in 7 (70%) pts.
Three of 5 (60%) evaluable pts responded at week 24. This included 3 (75%) symptom responses and 1 (20%) spleen response (1 pt with both). Six pts have completed 12 weeks of treatment with 1 spleen response and 2 symptoms responses (Figure 1). Among 6 pts with baseline splenomegaly who received 12 weeks of treatment, spleen volume decreased in 5 (83%) by an average of -23% (+5% to -71%). Among 5 pts with significant baseline symptom burden who received 12 weeks of treatment, 4 (80%) experienced an improvement in symptom burden by an average of -43% (range 0% to -76%). One pt who discontinued treatment prior to week 8 for reasons unrelated to disease or treatment was considered a spleen and symptom non-responder despite experiencing a 48% symptom improvement at week 4.
At baseline, C-Myc expression was demonstrated by IHC staining in a median of 10% of cells (5-15%). Average baseline c-Myc expression product (% positive cells * staining intensity) was 26.5 (range 10-37.5). In pts with paired samples (n = 4), c-Myc expression product decreased in all cases by an average of 51% (25%-85%), p = 0.02.
Ten pts were evaluable for safety. The most common AEs occurring in >2 pts were anemia, platelet count decrease, diarrhea, nausea, muscle cramp, and constipation. Grade ≥3 AEs were anemia (40%) and neutropenia (10%). There were no grade ≥ 3 non-hematologic AEs. Two pts discontinued study treatment: one due to disease progression after initial response and one due to pt decision unrelated to disease or treatment.
Conclusion: Fedratinib demonstrates promising clinical efficacy in MDS/MPN and CNL pts with proliferative features. The safety profile is consistent with prior experience. Fedratinib's unique kinase inhibition profile may provide a mechanism for enhanced effectiveness in this pt population. Updated results will be presented at the meeting.