An updated review of the JAK1/2 inhibitor (ruxolitinib) in the Philadelphia-negative myeloproliferative neoplasms

Future Oncol. 2018 Jan;14(2):137-150. doi: 10.2217/fon-2017-0298. Epub 2017 Oct 23.

Abstract

Ruxolitinib (Rux), a JAK1/2 inhibitor, has been approved for patients with myelofibrosis and in polycythemia vera with inadequate response/intolerance to hydroxycarbamide. Studies have demonstrated that Rux improves disease-related symptoms and splenomegaly. A late emerging observation from two Phase III trials was that Rux was associated with survival advantage in comparison with placebo or other available therapies in myelofibrosis. Important data suggest that for polycythemia vera Rux improved control of blood counts. Main hematological side effects are anemia and thrombocytopenia predominantly at the beginning of the treatment. Some studies and case reports highlighted potential risks of nonmelanoma skin cancers and increased risk of infection including reactivation of hepatitis B, tuberculosis or herpes zoster infections after Rux treatment.

Keywords: myelofibrosis; myeloproliferative neoplasm; polycythemia vera; ruxolitinib.

MeSH terms

  • Aged
  • Animals
  • Blood Cell Count
  • Clinical Trials, Phase III as Topic
  • Disease Models, Animal
  • Disease-Free Survival
  • Drug-Related Side Effects and Adverse Reactions / classification
  • Drug-Related Side Effects and Adverse Reactions / pathology*
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Hydroxyurea / adverse effects
  • Janus Kinase 1 / antagonists & inhibitors
  • Janus Kinase 1 / genetics
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics
  • Male
  • Mice
  • Middle Aged
  • Myelodysplastic-Myeloproliferative Diseases / drug therapy*
  • Myelodysplastic-Myeloproliferative Diseases / genetics
  • Myelodysplastic-Myeloproliferative Diseases / pathology
  • Nitriles
  • Philadelphia Chromosome
  • Polycythemia Vera / drug therapy*
  • Polycythemia Vera / genetics
  • Polycythemia Vera / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / therapeutic use*
  • Pyrimidines
  • Treatment Outcome

Substances

  • BCR-ABL1 fusion protein, human
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Fusion Proteins, bcr-abl
  • Janus Kinase 1
  • Janus Kinase 2
  • Hydroxyurea