Safety and efficacy of fedratinib in patients with myelofibrosis previously treated with ruxolitinib: primary analysis of FREEDOM trial

• Published in: Leukemia & lymphoma 2024-09, Vol.65 (9), p.1314-1324
• Main Authors: Gupta, Vikas, Yacoub, Abdulraheem, Mesa, Ruben A, Harrison, Claire N, Vannucchi, Alessandro M, Kiladjian, Jean-Jacques, Deeg, Hans-Joachim, Fazal, Salman, Foltz, Lynda, Mattison, Ryan J, Miller, Carole B, Parameswaran, Vinod, Brown, Patrick, Hernandez, Christopher, Wang, Jia, Talpaz, Moshe
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Benzenesulfonamides; COVID-19 - epidemiology; Female; Humans; Male; Middle Aged; Nitriles; Primary Myelofibrosis - diagnosis; Primary Myelofibrosis - drug therapy; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Pyrrolidines - therapeutic use; SARS-CoV-2; Spleen - drug effects; Spleen - pathology; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Treatment Outcome
• ISSN: 1042-8194; 1029-2403; 1029-2403
• DOI: 10.1080/10428194.2024.2346733

The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet count ≥50 × 10 /L, previously treated with ruxolitinib. The trial design included protocol specified strategies to mitigate the risk for gastrointestinal (GI) adverse events (AEs), thiamine supplementation, and encephalopathy surveillance. Due to COVID-19, accrual was cut short with 38 patients enrolled. In the efficacy evaluable population (  = 35), nine (25.7%; 95% confidence interval 12.5-43.3) patients achieved primary endpoint of ≥35% spleen volume reduction (SVR) at end of cycle (EOC) 6; and 22 (62.9%) patients showed best overall response of ≥35% SVR up to end of treatment. Sixteen (44.4%) patients showed ≥50% reduction in total symptom score at EOC6 (  = 36). Compared to previously reported JAKARTA-2 trial, rates of GI AEs were lower, and no patient developed encephalopathy. Overall, FREEDOM study showed clinically relevant spleen and symptom responses with fedratinib, and effective mitigation of GI AEs.