Predictive models for splenic response to JAK-inhibitor therapy in patients with myelofibrosis

Leuk Lymphoma. 2019 Apr;60(4):1036-1042. doi: 10.1080/10428194.2018.1509315. Epub 2018 Sep 20.

Abstract

JAK inhibitors for myelofibrosis (MF) reduce spleen size, control constitutional symptoms, and may improve survival. We studied the clinical characteristics of 548 MF patients treated with JAK inhibitors from 2008 to 2016 to better understand predictors of splenic response. Response was defined as a 50% decrease in spleen size at early (3-4 months on therapy) and late (5-12 months) timepoints after therapy initiation. Early response positively correlated with higher doses of JAK inhibitor, baseline spleen size 5-10 cm, and hemoglobin. Early response negatively correlated with baseline spleen size >20 cm and high WBC. The strongest predictor of late response was whether a patient had a response at the earlier timepoint (OR 8.88). Our response models suggest that clinical factors can be used to predict which patients are more likely to respond to JAK inhibitors, and those who do not achieve an early response, i.e. within 3-4 months, should consider alternative treatments.

Keywords: JAK inhibitors; Myelofibrosis; myeloproliferative neoplasms; predictive models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Female
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Janus Kinase Inhibitors / administration & dosage
  • Janus Kinase Inhibitors / adverse effects
  • Janus Kinase Inhibitors / therapeutic use*
  • Male
  • Odds Ratio
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / etiology
  • Primary Myelofibrosis / metabolism
  • STAT Transcription Factors / metabolism
  • Signal Transduction / drug effects
  • Spleen / drug effects*
  • Spleen / pathology
  • Treatment Outcome

Substances

  • Janus Kinase Inhibitors
  • STAT Transcription Factors
  • Janus Kinase 2