6  JAK inhibitors in MDS_MPN

6.1 Pacritinib

6.2 Fedratinib

6.2.1 ASCO 2026 Abstract

  • phase 2 of fedratinib in 25 pts with proliferative MDS/MPN + CNL (aCML n=6, CNL n=5, MDS/MPN-RS-T n=6, MDS/MPN-U n=8)

  • Top 5 takeaways:

  1. Primary endpoint hit: 44% ORR @ wk 24 per MDS/MPN IWG; SVR35 30%, TSS50 47%, dual responders 25%

  2. CSF3R mutations enriched in SVR35 responders (4/6 = 67%) — strongest molecular biomarker signal; CNL-specific implication

  3. mPFS = mOS = 36.9 mo — strikingly better than ruxolitinib historical mOS 18.8 mo in CNL/aCML (but small n; disease-stratified: aCML 19.8 mo worst)

  4. Mechanism rationale: Fed = JAK2 + FLT3 + BRD4 → c-Myc suppression — broader kinase profile vs ruxolitinib

  5. Safety: SAEs 52%; thiamine deficiency n=1 (the classical fedratinib Wernicke encephalopathy signal); GI predominant