Abstract
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; 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 describe extended follow-up for patients in this study. After a median (range) follow-up of 26 months (0.53?36.7), best overall response rate (ORR) in the all treated population was 69% (29/42) with 13 (31%) patients who achieved a complete response and 16 (38%) patients who achieved 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; 6 of 10 patients (60%) with =3 involved organs showed responses in =3 organs. A total of 11 of 18 (61%) patients who had sclerosis at baseline showed a sclerotic response (39% complete response, 22% partial response). A total of 27 of 42 (64%) patients reached a corticosteroid dose of <0.15 mg/kg/day during the study; 8 responders discontinued corticosteroid treatment and remained off corticosteroid as of study closure. Safety findings for this updated analysis were consistent with the safety profile seen at the time of 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 (43%) patients. At a median follow-up of >2 years, ibrutinib continued to produce durable responses in patients with cGVHD that had failed prior systemic therapy. In this pretreated, high-risk population, clinically meaningful benefit and an acceptable safety profile was observed with additional follow-up for ibrutinib. These results demonstrate a substantial advance in the therapeutic management of patients with cGVHD.
View details for DOI 10.1016/j.bbmt.2019.06.023
View details for PubMedID 31260802