Ruxolitinib in steroid-refractory acute graft-vs-host disease: Japanese subgroup analysis of the randomized REACH2 trial

Int J Hematol. 2024 Jul;120(1):106-116. doi: 10.1007/s12185-024-03772-6. Epub 2024 May 25.

Abstract

Acute graft-versus-host disease (aGvHD) is a major complication after allogeneic hematopoietic stem cell transplantation in Japan and other countries. Nearly one-third of patients do not respond to standard systemic steroid therapy and no standard second-line treatment has been established in Japan. We report efficacy and safety findings of ruxolitinib versus best available therapy (BAT) from a subgroup analysis of the international, phase 3 REACH2 study in Japanese patients with steroid-refractory aGvHD. The primary endpoint was overall response rate (ORR) at day 28. Overall, 9 patients received ruxolitinib and 21 received BAT. The ORR at day 28 (88.9% vs 52.4%) and durable ORR at day 56 (66.7% vs 28.6%) were higher with ruxolitinib versus BAT. The estimated cumulative incidence of loss of response at 6 months was 12.5% with ruxolitinib and 18.2% with BAT. The median failure-free survival was longer with ruxolitinib versus BAT (2.73 vs 1.25 months). The most common adverse events up to day 28 in the ruxolitinib and BAT groups were anemia (55.6% vs 19.0%) and thrombocytopenia (44.4% vs 4.8%, respectively). Ruxolitinib showed better efficacy outcomes and a consistent safety profile compared with BAT in the Japanese subgroup, and the findings were consistent with overall study results.

Keywords: Acute graft-versus-host disease; JAK inhibitor; Japanese; Ruxolitinib.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • East Asian People
  • Female
  • Graft vs Host Disease* / drug therapy
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Nitriles*
  • Pyrazoles* / adverse effects
  • Pyrazoles* / therapeutic use
  • Pyrimidines* / therapeutic use
  • Steroids / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • ruxolitinib
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • Steroids