Ruxolitinib for steroid-refractory chronic graft-versus-host disease: Japanese subgroup analysis of REACH3 study

Int J Hematol. 2024 Dec;120(6):705-716. doi: 10.1007/s12185-024-03850-9. Epub 2024 Oct 3.

Abstract

Ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, has demonstrated safety and efficacy in patients with graft-versus-host disease (GvHD). This phase 3 randomized trial (REACH3) evaluated the efficacy and the safety of ruxolitinib 10 mg twice daily compared with investigator-selected best available therapy (BAT) in a subgroup of Japanese patients (n = 37) with steroid-refractory or dependent (SR/D) chronic GvHD. At data cut-off, treatment was ongoing in 17 patients and discontinued in 20. The overall response rate (complete or partial) at week 24 was greater with ruxolitinib than BAT (50% vs. 20%; odds ratio, 4.13 [95% CI, 0.90-18.9]). The best overall response rate (complete or partial response at any time point up to week 24) was higher with ruxolitinib than BAT (68.2% vs. 46.7%; odds ratio, 2.69 [95% CI, 0.66-10.9]). Ruxolitinib led to longer median failure-free survival than BAT (18.6 months vs. 3.7 months; hazard ratio, 0.34; [95% CI, 0.14-0.85]). The most common grade ≥ 3 adverse events up to week 24 were anemia (ruxolitinib: 22.7%; BAT: 6.7%) and pneumonia (22.7% and 20.0%, respectively). Ruxolitinib showed a higher response rate and improvement in failure-free survival in Japanese patients with SR/D chronic GvHD, with a safety profile consistent with the overall study population.

Keywords: Chronic graft-versus-host disease; JAK inhibitor; Japanese; REACH3; Ruxolitinib.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chronic Disease
  • East Asian People
  • Female
  • Graft vs Host Disease* / drug therapy
  • Graft vs Host Disease* / etiology
  • 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