TY - JOUR
T1 - An open-label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid-dependent/steroid-resistant chronic GVHD
AU - Inamoto, Yoshihiro
AU - Kato, Koji
AU - Kawakita, Toshiro
AU - Onishi, Yasushi
AU - Matsuoka, Ken ichi
AU - Shiratori, Soichi
AU - Ikegame, Kazuhiro
AU - Hiramoto, Nobuhiro
AU - Toyosaki, Masako
AU - Katayama, Yuta
AU - Murayama, Shun
AU - Sasagawa, Yuji
AU - Maeda, Yoshinobu
AU - Hatake, Kiyohiko
AU - Teshima, Takanori
N1 - Publisher Copyright:
© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2024/10
Y1 - 2024/10
N2 - Belumosudil mesylate is a selective Rho-associated coiled-coil kinase 2 inhibitor with immunomodulatory and antifibrosis effects. This multicenter, open-label, single-arm study evaluated belumosudil 200 mg once daily as second or subsequent line of therapy (LOT) in 21 Japanese patients ≥12 years of age with steroid-dependent/steroid-resistant chronic graft-versus-host disease (cGVHD). The primary endpoint of best overall response rate (ORR) at 24 weeks after enrollment of the last patient was 85.7% (95% confidence interval [CI]: 63.7–97.0), and the lower limit of the 95% CI exceeded the pre-defined threshold of 25%. The Kaplan–Meier estimate of duration of response rate at 24 weeks was 75% (95% CI: 46–90); 13/18 responders (72.2%) had a sustained response for ≥20 weeks. The median time to response was 4.1 weeks (range 3.90–8.10); ORR was 47.6% at 4 weeks and 75.0% at 24 weeks; best ORR was 80% for joints/fascia, 66.7% for the mouth, and 54.5% for skin. Overall, 57.1% of patients had clinically meaningful symptom improvement at least once; the median duration of symptom improvement was 22.2 weeks (range 4.0–51.3). Corticosteroid dose reductions were recorded for 57.1% of patients. Median failure-free and overall survival were not reached. Treatment-emergent adverse events occurred in 85.7% of patients (most commonly diarrhea, 19.0%), of which 38.1% were drug-related. There were no drug-related discontinuations or deaths. In summary, belumosudil 200 mg once daily as second or subsequent LOT in Japanese patients with steroid-dependent/steroid-resistant cGVHD was effective, with no new safety concerns.
AB - Belumosudil mesylate is a selective Rho-associated coiled-coil kinase 2 inhibitor with immunomodulatory and antifibrosis effects. This multicenter, open-label, single-arm study evaluated belumosudil 200 mg once daily as second or subsequent line of therapy (LOT) in 21 Japanese patients ≥12 years of age with steroid-dependent/steroid-resistant chronic graft-versus-host disease (cGVHD). The primary endpoint of best overall response rate (ORR) at 24 weeks after enrollment of the last patient was 85.7% (95% confidence interval [CI]: 63.7–97.0), and the lower limit of the 95% CI exceeded the pre-defined threshold of 25%. The Kaplan–Meier estimate of duration of response rate at 24 weeks was 75% (95% CI: 46–90); 13/18 responders (72.2%) had a sustained response for ≥20 weeks. The median time to response was 4.1 weeks (range 3.90–8.10); ORR was 47.6% at 4 weeks and 75.0% at 24 weeks; best ORR was 80% for joints/fascia, 66.7% for the mouth, and 54.5% for skin. Overall, 57.1% of patients had clinically meaningful symptom improvement at least once; the median duration of symptom improvement was 22.2 weeks (range 4.0–51.3). Corticosteroid dose reductions were recorded for 57.1% of patients. Median failure-free and overall survival were not reached. Treatment-emergent adverse events occurred in 85.7% of patients (most commonly diarrhea, 19.0%), of which 38.1% were drug-related. There were no drug-related discontinuations or deaths. In summary, belumosudil 200 mg once daily as second or subsequent LOT in Japanese patients with steroid-dependent/steroid-resistant cGVHD was effective, with no new safety concerns.
UR - http://www.scopus.com/inward/record.url?scp=85197463751&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85197463751&partnerID=8YFLogxK
U2 - 10.1002/ajh.27424
DO - 10.1002/ajh.27424
M3 - Article
AN - SCOPUS:85197463751
SN - 0361-8609
VL - 99
SP - 1917
EP - 1926
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 10
ER -