Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study
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- Corey Cutler
- Division of Transplantation and Cellular Therapy, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;
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- Stephanie J. Lee
- Fred Hutchinson Cancer Research Center, Seattle, WA;
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- Sally Arai
- Stanford University Medical Center, Stanford, CA;
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- Marcello Rotta
- Colorado Blood Cancer Institute, Denver, CO;
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- Behyar Zoghi
- Texas Transplant Institute, Methodist Hospital, San Antonio, TX;
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- Aleksandr Lazaryan
- Moffitt Cancer Center, Tampa, FL;
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- Aravind Ramakrishnan
- St David’s South Austin Medical Center, Austin, TX;
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- Zachariah DeFilipp
- Massachusetts General Hospital, Boston, MA;
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- Amandeep Salhotra
- City of Hope Medical Center, Duarte, CA;
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- Wanxing Chai-Ho
- University of California, Los Angeles Medical Center, Los Angeles, CA;
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- Rohtesh Mehta
- MD Anderson Cancer Center, Houston, TX;
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- Trent Wang
- University of Miami, Miami, FL;
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- Mukta Arora
- University of Minnesota Masonic Cancer Center, Minneapolis, MN;
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- Iskra Pusic
- Washington University School of Medicine, Saint Louis, MO;
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- Ayman Saad
- The Ohio State University Wexner Medical Center, Columbus, OH;
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- Nirav N. Shah
- Froedtert Hospital and the Medical College of Wisconsin, Milwaukee, WI;
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- Sunil Abhyankar
- The University of Kansas Cancer Center, Fairway, KS;
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- Carlos Bachier
- Sarah Cannon Research Institute, Nashville, TN;
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- John Galvin
- University of Illinois at Chicago, Chicago, IL;
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- Annie Im
- University of Pittsburgh Medical Center–Hillman Cancer Center, Pittsburgh, PA;
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- Amelia Langston
- Winship Cancer Institute of Emory University, Atlanta, GA;
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- Jane Liesveld
- University of Rochester, Rochester, NY;
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- Mark Juckett
- University of Wisconsin Carbone Cancer Center, Madison, WI;
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- Aaron Logan
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA;
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- Levanto Schachter
- Oregon Health and Science University, Portland, OR;
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- Asif Alavi
- Barbara Ann Karmanos Cancer Institute, Detroit, MI;
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- Dianna Howard
- Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC;
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- Harlan W. Waksal
- Kadmon Corporation, New York, NY;
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- John Ryan
- Kadmon Corporation, New York, NY;
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- David Eiznhamer
- Kadmon Corporation, New York, NY;
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- Sanjay K. Aggarwal
- Kadmon Corporation, New York, NY;
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- Jonathan Ieyoub
- Kadmon Corporation, New York, NY;
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- Olivier Schueller
- Kadmon Corporation, New York, NY;
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- Laurie Green
- Kadmon Corporation, New York, NY;
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- Zhongming Yang
- Kadmon Corporation, New York, NY;
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- Heidi Krenz
- Kadmon Corporation, New York, NY;
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- Madan Jagasia
- Vanderbilt-Ingram Cancer Center, Nashville, TN;
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- Bruce R. Blazar
- University of Minnesota, Minneapolis, MN; and
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- Steven Pavletic
- Center for Cancer Research, National Cancer Institute, Bethesda, MD
抄録
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
収録刊行物
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- Blood
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Blood 138 (22), 2278-2289, 2021-12-02
American Society of Hematology