Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis

Eur J Haematol. 2018 Sep;101(3):305-317. doi: 10.1111/ejh.13099. Epub 2018 Jul 4.

Abstract

Introduction: Ruxolitinib is the first approved drug for treatment of myelofibrosis, but its impact of outcome after allogeneic stem cell transplantation (ASCT) is unknown.

Patients and methods: We reported on 159 myelofibrosis patients (pts) with a median age of 59 years (r: 28-74) who received reduced intensity ASCT between 2000 and 2015 in eight German centers from related (n = 23), matched (n = 86) or mismatched (n = 50) unrelated donors. Forty-six (29%) patients received ruxolitinib at any time point prior to ASCT. The median daily dose of ruxolitinib was 30 mg (range 10-40 mg) and the median duration of treatment was 4.9 months (range 0.4-39.1 months).

Results: Primary graft failure was seen in 2 pts (4%) in the ruxolitinib and 3 (2%) in the non-ruxolitinib group. Engraftment and incidence of acute GVHD grade II to IV and III/IV did not differ between groups (37% vs 39% and 19% vs 28%, respectively), nor did the non-relapse mortality at 2 years (23% vs 23%). A trend for lower risk of relapse was seen in the ruxolitinib group (9% vs 17%, P = .2), resulting in a similar 2 year DFS and OS (68% vs 60% and 73% vs 70%, respectively). No difference in any outcome variable could be seen between ruxolitinib responders and those who failed or lost response to ruxolitinib.

Conclusions: These results suggest that ruxolitinib pretreatment in myelofibrosis patient does not negatively influence outcome after allogeneic stem cell transplantation.

Keywords: JAK2; calreticulin; myelofibrosis; myeloproliferative neoplasm; reduced intensity allogeneic stem cell transplantation; ruxolitinib.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Combined Modality Therapy
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Nitriles
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / mortality
  • Primary Myelofibrosis / therapy*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyrimidines
  • Recurrence
  • Severity of Illness Index
  • Survival Analysis
  • Transplantation Chimera
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Biomarkers
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib