Between a rux and a hard place: evaluating salvage treatment and outcomes in myelofibrosis after ruxolitinib discontinuation

Ann Hematol. 2018 Mar;97(3):435-441. doi: 10.1007/s00277-017-3194-4. Epub 2017 Nov 30.

Abstract

Ruxolitinib is a JAK1/2 inhibitor that is effective in managing symptoms and splenomegaly related to myelofibrosis (MF). Unfortunately, many patients must discontinue ruxolitinib, at which time treatment options are not well defined. In this study, we investigated salvage treatment options and clinical outcomes among MF patients who received and discontinued ruxolitinib outside the context of a clinical trial. Among 145 patients who received ruxolitinib, 23 died while on treatment, 58 remained on treatment at time of analysis, leaving 64 people available for analysis. Development of cytopenias was the most common reason for discontinuation (38%) after median treatment time of 3.8 months (mo). The majority of patients received some form of salvage therapy after ruxolitinib discontinuation (n = 42; 66%), with allogeneic hematopoietic stem cell transplant (alloHSCT) (n = 17), being most commonly employed. Lenalidomide, thalidomide, hydroxyurea, interferon, and danazol were used with similar frequency. The response rate to salvage treatment was 26% (8 responses) and responses were most often seen with lenalidomide or thalidomide. Improved outcomes were observed in patients who underwent alloHSCT or received salvage therapy compared to those who did not receive additional therapy. Median overall survival (OS) after ruxolitinib discontinuation was 13 months. These findings show that salvage therapy can provide clinical responses after ruxolitinib discontinuation; however, these responses are rare and outcomes in this patient population are poor. This represents an area of unmet clinical need in MF.

Keywords: Myelofibrosis; Ruxolitinib.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Male
  • Middle Aged
  • Palliative Care
  • Primary Myelofibrosis / complications
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / mortality
  • Primary Myelofibrosis / therapy
  • Pyrazoles / therapeutic use*
  • Retrospective Studies
  • Salvage Therapy
  • Splenomegaly / drug therapy
  • Splenomegaly / etiology
  • Splenomegaly / mortality
  • Survival Analysis
  • Transplantation, Homologous
  • Treatment Outcome
  • Withholding Treatment*

Substances

  • INCB018424
  • Pyrazoles