Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study

• Published in: Blood Vol. 138; no. 22; pp. 2278 - 2289
• Main Authors: Cutler, Corey, Lee, Stephanie J., Arai, Sally, Rotta, Marcello, Zoghi, Behyar, Lazaryan, Aleksandr, Ramakrishnan, Aravind, DeFilipp, Zachariah, Salhotra, Amandeep, Chai-Ho, Wanxing, Mehta, Rohtesh, Wang, Trent, Arora, Mukta, Pusic, Iskra, Saad, Ayman, Shah, Nirav N., Abhyankar, Sunil, Bachier, Carlos, Galvin, John, Im, Annie, Langston, Amelia, Liesveld, Jane, Juckett, Mark, Logan, Aaron, Schachter, Levanto, Alavi, Asif, Howard, Dianna, Waksal, Harlan W., Ryan, John, Eiznhamer, David, Aggarwal, Sanjay K., Ieyoub, Jonathan, Schueller, Olivier, Green, Laurie, Yang, Zhongming, Krenz, Heidi, Jagasia, Madan, Blazar, Bruce R., Pavletic, Steven
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02-12-2021; American Society of Hematology
• Subjects: Acetamides - administration & dosage; Acetamides - adverse effects; Acetamides - therapeutic use; Adult; Aged; Female; Graft vs Host Disease - drug therapy; Humans; Male; Middle Aged; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; rho-Associated Kinases - antagonists & inhibitors; Transplantation; Treatment Outcome; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2021012021

Belumosudil, an investigational oral selective inhibitor of Rho-associated coiled-coil–containing protein kinase 2 (ROCK2), reduces type 17 and follicular T helper cells via downregulation of STAT3 and enhances regulatory T cells via upregulation of STAT5. Belumosudil may effectively treat patients with chronic graft-versus-host disease (cGVHD), a major cause of morbidity and late nonrelapse mortality after an allogeneic hematopoietic cell transplant. This phase 2 randomized multicenter registration study evaluated belumosudil 200 mg daily (n = 66) and 200 mg twice daily (n = 66) in subjects with cGVHD who had received 2 to 5 prior lines of therapy. The primary end point was best overall response rate (ORR). Duration of response (DOR), changes in Lee Symptom Scale score, failure-free survival, corticosteroid dose reductions, and overall survival were also evaluated. Overall median follow-up was 14 months. The best ORR for belumosudil 200 mg daily and 200 mg twice daily was 74% (95% confidence interval [CI], 62-84) and 77% (95% CI, 65-87), respectively, with high response rates observed in all subgroups. All affected organs demonstrated complete responses. The median DOR was 54 weeks; 44% of subjects have remained on therapy for ≥1 year. Symptom reduction with belumosudil 200 mg daily and 200 mg twice daily was reported in 59% and 62% of subjects, respectively. Adverse events (AEs) were consistent with those expected in patients with cGVHD receiving corticosteroids and other immunosuppressants. Sixteen subjects (12%) discontinued belumosudil because of possible drug-related AEs. Belumosudil, a promising therapy for cGVHD, was well tolerated with clinically meaningful responses. This trial was registered at www.clinicaltrials.gov as #NCT03640481.
•Belumosudil, a selective ROCK2 inhibitor, was well tolerated in heavily pretreated subjects, with 44% continuing treatment beyond 1 year.•Belumosudil demonstrated efficacy in patients with SR cGVHD, with responses in all organs and after failure of ibrutinib/ruxolitinib.
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