Itacitinib for prevention of graft-versus-host disease and cytokine release syndrome in haploidentical transplantation
Abstract
Abstract Haploidentical hematopoietic cell transplantation (haplo-HCT) is an increasingly used treatment for hematologic malignancies. Although posttransplant cyclophosphamide (PtCy) has improved graft-versus-host disease (GVHD) prophylaxis in haplo-HCT, patients continue to experience life-threatening complications. Interferon gamma and interleukin-6 are central in the pathophysiology of GVHD and cytokine release syndrome (CRS), and both cytokines signal through Janus kinase 1 (JAK-1). We tested the effect of adding the JAK-1 selective inhibitor, itacitinib, to PtCy–haplo-HCT to mitigate these complications and improve overall survival (OS). This open-label, single-arm study evaluated the safety and efficacy of itacitinib combined with standard GVHD prophylaxis after haplo-HCT. A total of 42 patients were treated with itacitinib 200 mg daily from day −3 through +100 or +180, followed by a taper. Itacitinib resulted in low CRS grades, all patients had grade 0 (22%) or grade 1 (78%) CRS and there were no cases of grade 2 to 5 CRS. There were no cases of primary graft failure. No patients developed grade 3 to 4 acute GVHD (aGVHD) through day +180. The cumulative incidence of grade 2 aGVHD at day +100 was 21.9%. The 1-year cumulative incidence of moderate or severe chronic GVHD was 5%. The cumulative incidence of relapse at 2 years was 14%. OS at 1 year was 80%. The cumulative incidence of nonrelapse mortality (NRM) at day 180 was 8%. Itacitinib, when added to standard GVHD prophylaxis, was well tolerated and resulted in low rates of CRS, acute and chronic GVHD, and NRM, and encouraging rates of GVHD-free relapse-free survival and OS after haplo-HCT. This trial was registered at www.ClinicalTrials.gov as #NCT03755414.
Article Details
Authors (19)
Ramzi Abboud
4Washington University St Louis, St Louis, United States
Mark A. Schroeder
5Bone Marrow Transplantation and Leukemia Section, Division of Oncology, Washington University School of Medicine in Saint Louis, Saint Louis, MO
Michael P. Rettig
1Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
Reyka G. Jayasinghe
1Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
Feng Gao
Jeremy Eisele
1Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
Leah Gehrs
1University of Alabama at Birmingham, Pathology, Birmingham, United States
Julie Ritchey
1Washington University in St. Louis, St. Louis, United States
Jaebok Choi
1Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
Camille N. Abboud
1Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
Iskra Pusic
6Washington University in St. Louis School of Medicine, St. Louis, United States
Meagan Jacoby
1Washington University School of Medicine in St Louis, Hematology-Oncology, St Louis, United States
Peter Westervelt
11Massachusetts General Hospital, Boston, United States
Matthew Christopher
1Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
Amanda Cashen
1Washington University School of Medicine, Division of Oncology, St Louis, United States
Armin Ghobadi
5Washington University School of Medicine, St. Louis, United States
Keith Stockerl-Goldstein
1Washington University School of Medicine, Division of Oncology, Department of Medicine, Saint Louis, United States
Geoffrey L. Uy
Division of Oncology, Washington University School of Medicine, Saint Louis, Missouri, United States
John F. DiPersio
Department of Medicine, Washington University School of Medicine, St. Louis