Efficacy and tolerability of Janus kinase inhibitors in myelofibrosis: a systematic review and network meta-analysis

Blood Cancer J. 2021 Jul 27;11(7):135. doi: 10.1038/s41408-021-00526-z.

Abstract

Myelofibrosis is a myeloproliferative neoplasm associated with constitutional symptoms, increasing splenomegaly, and worsening cytopenias. Janus kinase (JAK) inhibitors have been used for the treatment of myelofibrosis for several years, but there is a lack of comparative information between those treatments. A systematic review and network meta-analysis was performed on randomized controlled trials in patients with myelofibrosis receiving JAK inhibitor or placebo or control. Primary outcomes were efficacy on spleen volume reduction and total symptom score reduction. Additional analyses were conducted on anemia and thrombopenia events. Seven studies were included in the network meta-analysis including 1953 patients randomly assigned to four JAK inhibitors-ruxolitinib, fedratinib, pacritinib, momelotinib-or control. In first-line therapy, momelotinib and fedratinib were associated with comparable efficacy to ruxolitinib, and with less toxicity on erythrocytes and platelets, respectively. Pacritinib was less effective on splenomegaly than ruxolitinib as a first-line treatment but seemed effective in second line, after ruxolitinib exposure. Fedratinib and ruxolitinib that are FDA approved in myelofibrosis have both confirmed being valuable option to treat splenomegaly and constitutional symptoms, and their slightly different tolerance-profiles can guide therapeutic choice for first-line treatment, according to patient profile. Momelotinib could be another option especially due to its positive effect on anemia.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Bridged-Ring Compounds / adverse effects
  • Bridged-Ring Compounds / therapeutic use
  • Humans
  • Janus Kinase Inhibitors / adverse effects
  • Janus Kinase Inhibitors / therapeutic use*
  • Nitriles / adverse effects
  • Nitriles / therapeutic use
  • Primary Myelofibrosis / complications
  • Primary Myelofibrosis / drug therapy*
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use
  • Pyrrolidines / adverse effects
  • Pyrrolidines / therapeutic use
  • Splenomegaly / complications
  • Splenomegaly / drug therapy
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use
  • Treatment Outcome

Substances

  • 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene
  • Bridged-Ring Compounds
  • Janus Kinase Inhibitors
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • Pyrrolidines
  • Sulfonamides
  • fedratinib
  • ruxolitinib