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

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

Souichi Shiratori  1 , Kentaro Fukushima  2 , Yasushi Onishi  3 , Noriko Doki  4 , Tatsunori Goto  5 , Masaya Okada  6 , Hirohisa Nakamae  7 , Yoshinobu Maeda  8 , Koji Kato  9 , Takayuki Ishikawa  10 , Tadakazu Kondo  10   11 , Masako Toyosaki  12 , Takashi Ikeda  13 , Naoyuki Uchida  14 , Akio Maki  15 , Fumika Shimada  15 , Takeshi Tajima  15 , Tommaso Stefanelli  16 , Takanori Teshima  17
Affiliations
Clinical Trial

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

Souichi Shiratori et al. Int J Hematol. 2024 Dec.

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.

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Conflict of interest statement

Declarations. Conflict of interest: SS, ND, MO, TK, TIshikawa and TIkeda have nothing to disclose. KF and MT received honoraria from Janssen. YO received honoraria from Novartis, Pfizer, Janssen, AsahiKasei, Abbvie, Astellas, Amgen, Chugai, Bristol-Myers Squibb, Symbio, MSD, Meiji Seika, Sumitomo Dainippon, Daiichi Sankyo, Nippon Shinyaku, IQVIA, KISSEI and Kyowa Kirin; research funding from Novartis, Pfizer, Janssen, Meiji Seika, Incyte, and Takara Bio. TG received honoraria from Novartis and Mallinckrodt. HN received honoraria from Novartis, Janssen, Chugai, Astellas, Bristol-Myers Squibb and Takeda; research funding from Novartis, Astellas, Bristol-Myers Squibb and Takeda. YM received research funding from from Asahi Kasei, Eisai, Otsuka, Kyowa Kirin, Taiho, Takeda, Chugai, Japan blood products, Nippon Kayaku, Nippon Shinyaku, Mallinckrodt, and Regimmune; and honoraria from Asahi Kasei, AstraZeneca, Astellas, Amgen, AbbVie, Viatris, Eisai, MSD, Otsuka, ONO, Gilead, Kyorin, Kyowa, Kissei, Konica, Sanofi, Celgene, Bristol-Myers Squibb, Bayer, CSL Behring, Daiichi Sankyo, Sumitomo Dainippon, Takeda, Terumo, Chugai, Nippon Shinyaku, Novartis, Pfizer, Mundipharma, Human Life CORD, Meiji Seika, Janssen and Yakult Honsha. KK received consulting fees from AbbVie, AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Janssen, and Novartis; honoraria from Bristol-Myers Squibb, Chugai, Sumitomo Pharma Co., Ltd., Janssen, Kyowa Kirin, MSD, Novartis and ONO; and research funding from AbbVie, MSD, Bristol-Myers Squibb, Janssen, Novartis, Chugai, Daiichi Sankyo, Eisai, Kyowa Kirin, and ONO. NU received honoraria from Novartis and Otsuka. AM, FS and TT are employees of Novartis Pharma K.K., Tokyo, Japan. TS is an employee of Novartis Pharma AG, Basel, Switzerland. TTeshima received honoraria from Novartis, Abbvie, Astellas, NIPPON SHINYAKU, Kyowa Kirin, Bristol-Myers Squibb, Sumitomo Pharma, Merck Sharp & Dohme, Celgene, Chugai, and Janssen; research funding from Astellas, Chugai, Fuji Pharma, Kyowa Kirin, Nippon Shinyaku, Asahi Kasei Pharma, Eisai, Sumitomo Pharma, ONO, Shionogi, Priothera SA, LUCA science and Otsuka; advisory board fees from Meiji Seika Pharma, Daiichi Sankyo, Asahi Kasei Pharma, Astellas, AstraZeneca, Takeda, Janssen, Toche Diagnostics, Sumitomo Pharma, Celgene, and Sanofi.

Figures

Fig. 1
Fig. 1
Patient disposition. *Ongoing treatment and/or assessments during the main treatment period at the data cut-off date May 08, 2020. AE adverse events, BAT best available therapy, MMF mycophenolate mofetil
Fig. 2
Fig. 2
a Overall response rate (ORR) and b best overall response (BOR) up to week 24. a Overall response rate at week 24. ORR is defined as proportion of patients who achieved CR or PR according to 2014 NIH consensus criteria. b Best overall response rate up to week 24. BOR is defined as proportion of patients who achieved CR or PR at any time point up to week 24 or the start of additional systemic therapy for cGvHD. BAT best available therapy, BOR best overall response, CR complete response, n number of patients who are at the corresponding category, OR odds ratio, ORR overall response rate, PR partial response
Fig. 3
Fig. 3
Kaplan–Meier estimate of failure-free survival (FFS) at week 24. BAT best available therapy, BID twice a day, FFS failure-free survival, RUX ruxolitinib. FFS is defined as time from the date of randomization to the earliest of recurrence of underlying disease, start of new systemic treatment for cGvHD, or death
Fig. 4
Fig. 4
Change from baseline in summary symptom score (mLSS) at week 24. Change from baseline calculated for patients with available data at baseline and the corresponding post baseline timepoint. *Patients with change of or addition of new systemic cGvHD treatment are counted as non-responders irrespective of the TSS value. BAT best available therapy, cGvHD chronic graft-versus-host disease, mLSS modified Lee cGvHD symptom scale, RUX ruxolitinib, TSS total symptom score
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