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

• Published in: International journal of hematology 2024-12, Vol.120 (6), p.705-716
• Main Authors: Shiratori, Souichi, Fukushima, Kentaro, Onishi, Yasushi, Doki, Noriko, Goto, Tatsunori, Okada, Masaya, Nakamae, Hirohisa, Maeda, Yoshinobu, Kato, Koji, Ishikawa, Takayuki, Kondo, Tadakazu, Toyosaki, Masako, Ikeda, Takashi, Uchida, Naoyuki, Maki, Akio, Shimada, Fumika, Tajima, Takeshi, Stefanelli, Tommaso, Teshima, Takanori
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anemia; Chronic Disease; East Asian People; Effectiveness; Female; Graft versus host disease; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Graft-versus-host reaction; Hematology; Humans; Janus kinase; Janus kinase 2; Japan; Kinases; Male; Medicine; Medicine & Public Health; Middle Aged; Nitriles; Oncology; Original; Original Article; Population studies; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - therapeutic use; Response rates; Safety; Steroids; Steroids - therapeutic use; Subgroups; Survival; Treatment Outcome; Young Adult
• ISSN: 0925-5710; 1865-3774; 1865-3774
• DOI: 10.1007/s12185-024-03850-9

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.