Novel therapeutic agents for myelofibrosis after failure or suboptimal response to JAK2 inhbitors

Curr Opin Oncol. 2022 Nov 1;34(6):729-737. doi: 10.1097/CCO.0000000000000898. Epub 2022 Aug 26.

Abstract

Purpose of review: JAK2 inhibitors have changed the therapeutic strategies for the management of primary and secondary myelofibrosis. Ruxolitinib, the first available agent, improved disease-related symptoms, spleen volume, and overall survival compared to conventional chemotherapy. It has been revealed that after 3 years of treatment, about 50% of patients discontinued ruxolitinib for resistance and/or intolerance and should be candidate to a second line of treatment.

Recent findings: Second-generation tyrosine kinase inhibitors have been tested in this setting, but all these new drugs do not significantly impact on disease progression. Novel agents are in developments that target on different pathways, alone or in combination with JAK2 inhibitors.

Summary: In this review, we summarize all the clinical efficacy and safety data of these drugs providing a vision of the possible future.

Publication types

  • Review

MeSH terms

  • Humans
  • Janus Kinase 2* / antagonists & inhibitors
  • Nitriles / therapeutic use
  • Primary Myelofibrosis* / chemically induced
  • Primary Myelofibrosis* / drug therapy
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyrazoles / therapeutic use
  • Pyrimidines / therapeutic use

Substances

  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • JAK2 protein, human
  • Janus Kinase 2