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Biol Blood Marrow Transplant. 2019 Jun 28. pii: S1083-8791(19)30407-0. doi: 10.1016/j.bbmt.2019.06.023. [Epub ahead of print]

Ibrutinib for Chronic Graft-versus-Host Disease After Failure of Prior Therapy: 1-Year Update of a Phase 1b/2 Study.

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Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia. Electronic address:
Department of Medicine, Medicine/BMT Division, Stanford University School of Medicine, Stanford, California.
Division of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
Department of Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, Minnesota.
Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
Division of Oncology, BMT and Leukemia Section, Washington University School of Medicine, St. Louis, Missouri.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, University of California San Francisco, San Francisco, California.
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California.
Department of Biostatistics, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California.
Department of Biometrics and Data Management, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California.
Department of Clinical Science, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California.
Division of Hematology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, Ohio.


Chronic graft-versus-host disease (cGVHD) is a life-threatening complication of allogeneic stem cell transplantation. In a Phase 1b/2, open-label study (PCYC-1129; identifier NCT02195869) involving 42 patients with active cGVHD who were steroid-dependent or -refractory, the activity and safety of ibrutinib, a once-daily inhibitor of Bruton's tyrosine kinase, was demonstrated. Here we report extended follow-up for patients in this study. After a median follow-up of 26 months (range, .53 to 36.7 months), best overall response rate in the all treated population was 69% (29 of 42), with 13 patients (31%) achieving a complete response and 16 patients (38%) achieving a partial response. Sustained responses of ≥20, ≥32, and ≥44 weeks were seen in 20 (69%), 18 (62%), and 16 (55%) of the 29 responders, respectively. Of 26 patients with ≥2 involved organs, 19 (73%) showed responses in ≥2 organs. Six of 10 patients (60%) with ≥3 involved organs showed responses in ≥3 organs. Eleven of 18 patients (61%) who had sclerosis at baseline showed a sclerotic response (39% with complete response, 22% with partial response). Twenty-seven of 42 patients (64%) reached a corticosteroid dose of <.15 mg/kg/day during the study; 8 discontinued corticosteroid treatment and remained off corticosteroid at study closure. Safety findings for this updated analysis were consistent with the safety profile seen at the time of the original analysis. Common grade ≥3 adverse events (AEs) were pneumonia (n = 6), fatigue (n = 5), and diarrhea (n = 4). The onset of new grade ≥3 AEs decreased from 71% in the first year of treatment to 25% in the second year (n = 12). AEs leading to discontinuation occurred in 18 patients (43%). At a median follow-up of >2 years, ibrutinib continued to produce durable responses in patients with cGVHD who had failed previous systemic therapy. In this pretreated, high-risk population, clinically meaningful benefit and an acceptable safety profile were observed with additional follow-up for ibrutinib. These results demonstrate a substantial advance in the therapeutic management of patients with cGVHD.


Bruton's tyrosine kinase inhibitor; Chronic graft-versus-host disease; Ibrutinib; Steroid-dependent chronic graft-versus-host disease; Steroid-refractory chronic graft versus host disease

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