Low rates of chronic graft-versus-host disease with ruxolitinib maintenance following allogeneic HCT
Abstract
Abstract Despite recent advances in graft-versus-host disease (GVHD) prophylaxis, novel approaches to effective prevention of chronic GVHD (cGVHD) remain of high importance. In this prospective, multicenter, phase 2 trial, ruxolitinib, an oral inhibitor of Janus kinase (JAK) 1 and 2, was administered as maintenance therapy after reduced-intensity allogeneic hematopoietic cell transplantation (HCT). GVHD prophylaxis consisted of tacrolimus and methotrexate. Ruxolitinib began between day +30 to 100 and was administered continuously in 28-day cycles for up to 24 cycles. Seventy-eight participants were enrolled before HCT; 63 participants received the intervention. The median start date of ruxolitinib after HCT was day +45. The most common grade ≥3 adverse events were neutropenia, thrombocytopenia, and anemia. Seven participants experienced grade ≥3 infectious events. GVHD-free, relapse-free survival at 1 year after HCT, the primary end point, was 70%. Grade 3 to 4 acute GVHD at 6 months was 4.8%, and moderate-severe cGVHD at 2 years was 16%. cGVHD requiring systemic therapy was 9.5% at 1 year and 13% at 2 years. Overall survival and progression-free survival at 2 years were 76% and 68%, respectively. Prolonged administration of ruxolitinib following HCT is associated with low rates of clinically significant cGVHD. The incorporation of JAK inhibition into GVHD prevention approaches warrants further investigation. This trial was registered at www.clinicaltrials.gov as #NCT03286530.
Article Details
Authors (19)
Zachariah Defilipp
7Massachusetts General Hospital, Hematopoietic Cell Transplant and Cellular Therapy Program, Boston, United States
Haesook T. Kim
2Department of Data Science, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA
Laura W. Knight
3Cancer Center Protocol Office, Massachusetts General Hospital, Boston, MA
Suzanne M. O’Connor
3Cancer Center Protocol Office, Massachusetts General Hospital, Boston, MA
Shilton E. Dhaver
3Cancer Center Protocol Office, Massachusetts General Hospital, Boston, MA
Meghan White
3Cancer Center Protocol Office, Massachusetts General Hospital, Boston, MA
Bhagirathbhai Dholaria
Mark A. Schroeder
5Bone Marrow Transplantation and Leukemia Section, Division of Oncology, Washington University School of Medicine in Saint Louis, Saint Louis, MO
Sumithira Vasu
29Department of Internal Medicine, The Ohio State University, Columbus, OH
Sameem Abedin
1Medical College of Wisconsin, Medicine - Hematology/Oncology, Milwaukee, United States
Jooho Chung
1Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA
Areej El-Jawahri
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Matthew J. Frigault
3Massachusetts General Hospital, Boston, MA
Steven McAfee
1Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA
Richard A. Newcomb
1Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA
Paul V. O’Donnell
1Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA
Thomas R. Spitzer
Department of Medicine, Harvard Medical School, Boston
Yi-Bin Chen
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Gabriela S. Hobbs
10Department of Hematology-Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA