Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia

Haematologica. 2022 Jul 1;107(7):1599-1607. doi: 10.3324/haematol.2021.279415.


Thrombocytopenia is common in patients with myelofibrosis (MF) and is a well-established adverse prognostic factor. Both of the approved Janus kinase (JAK) inhibitors, ruxolitinib and fedratinib, can worsen thrombocytopenia and have not been evaluated in patients with severe thrombocytopenia (platelet counts <50×109/L). Pacritinib, a novel JAK2/interleukin-1 receptor-associated kinase 1 inhibitor, has been studied in two phase III trials (PERSIST-1 and PERSIST- 2), both of which enrolled patients with MF and severe thrombocytopenia. In order to better characterize treatment outcomes for this population with advanced disease, we present a retrospective analysis of efficacy and safety data in the 189 patients with severe thrombocytopenia treated in the PERSIST studies. The proportion of patients in the pacritinib group meeting efficacy endpoints was greater than in the BAT group for ≥35% spleen volume reduction (23% vs. 2%, P=0.0007), ≥50% modified Total Symptom Score reduction (25% vs. 8%, P=0.044), and self-reported symptom benefit ("much" or "very much" improved; 25% vs. 8%, P=0.016) at the primary analysis time point (week 24). The adverse event profile of pacritinib was manageable, and dose modification was rarely required. There was no excess in bleeding or death in pacritinib-treated patients. These results indicate that pacritinib is a promising treatment for patients with MF who lack safe and effective therapeutic options due to severe thrombocytopenia.

Trial registration: NCT02055781 NCT04884191.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia* / chemically induced
  • Bridged-Ring Compounds
  • Humans
  • Janus Kinase 2
  • Nitriles / therapeutic use
  • Primary Myelofibrosis* / complications
  • Primary Myelofibrosis* / diagnosis
  • Primary Myelofibrosis* / drug therapy
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines
  • Retrospective Studies
  • Thrombocytopenia* / chemically induced
  • Thrombocytopenia* / etiology


  • 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene
  • Bridged-Ring Compounds
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Janus Kinase 2

Associated data