Differences in presenting features, outcome and prognostic models in patients with primary myelofibrosis and post-polycythemia vera and/or post-essential thrombocythemia myelofibrosis treated with ruxolitinib. New perspective of the MYSEC-PM in a large multicenter study

Semin Hematol. 2018 Oct;55(4):248-255. doi: 10.1053/j.seminhematol.2018.05.013. Epub 2018 Jun 5.

Abstract

Recently, the myelofibrosis secondary to PV and ET prognostic model (MYSEC-PM) was introduced to assess prognosis in myelofibrosis (MF) secondary to polycythemia vera and essential thrombocythemia (post-PV and post-ET MF), replacing the International Prognostic Scoring System (IPSS) and/or Dynamic IPSS (DIPSS) that was applied for primary MF (PMF). In a cohort of 421 ruxolitinib (RUX)-treated patients (post-PV and post-ET MF: 44.2%), we evaluated the following: (1) disease phenotype, responses, and toxicity to RUX; and (2) performance of the MYSEC-PM in post-PV or post-ET MF. While the IPSS failed to correctly stratify post-PV or post-ET MF patients at diagnosis, the MYSEC-PM identified 4 risk categories projected at significantly different survival probability (P < .001). Additionally, the MYSEC-PM maintained a prognostic value in post-PV and post-ET MF also when used over time, at RUX start. Notably, the MYSEC-PM reclassified 41.8% and 13.6% of patients into a lower and higher risk category, respectively. Finally, patients at intermediate-1 risk had significantly higher spleen responses and lower hematological toxicities compared to higher risk patients. Compared to PMF, post-PV and post-ET MF presented a more hyperproliferative disease, with higher leukocyte and/or platelet count and hemoglobin levels both at diagnosis and at RUX start. Despite comparable response rates, post-PV and post-ET MF had lower rate of RUX-induced anemia and thrombocytopenia at 3 and 6 months. The study validates MYSEC-PM in post-PV and post-ET MF prognostication. Post-PV or post-ET MF represents a separate entity compared to PMF in terms of clinical manifestations and toxicity to RUX.

Keywords: IPSS; MYSEC-PM; Myelofibrosis; Risk scores; Ruxolitinib.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Janus Kinases / pharmacology
  • Janus Kinases / therapeutic use*
  • Polycythemia Vera / drug therapy*
  • Polycythemia Vera / mortality
  • Polycythemia Vera / pathology
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / mortality
  • Primary Myelofibrosis / pathology
  • Prognosis
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Survival Rate
  • Thrombocythemia, Essential / drug therapy*
  • Thrombocythemia, Essential / mortality
  • Thrombocythemia, Essential / pathology

Substances

  • INCB018424
  • Pyrazoles
  • Janus Kinases