Ibrutinib for the treatment of patients with chronic graft-versus-host disease after failure of one or more lines of systemic therapy

Drugs Today (Barc). 2018 May;54(5):305-313. doi: 10.1358/dot.2018.54.5.2807865.

Abstract

Chronic graft-versus-host disease (cGvHD) is a grave complication of allogeneic hematopoietic cell transplantation (alloHCT). Despite the use of prophylactic regimens for cGvHD, a significant proportion of patients develop cGvHD following alloHCT. The standard first-line therapy for cGvHD is high-dose corticosteroids. However, roughly 50% of patients will exhibit steroid-refractory or steroid-dependent cGvHD, which increases the risk of non-relapse mortality. Ibrutinib was approved by the U.S. Food and Drug Administration (FDA) in August 2017 for the treatment of cGvHD after failure of one or more lines of systemic therapy. The approval was based on a study that demonstrated high rates of sustained responses and manageable toxicities in patients with steroid-refractory or -dependent cGvHD. In this review, we address the mechanisms of action of ibrutinib in cGvHD, as well as preclinical and clinical data supporting its use in patients with this important post-transplant complication.

Keywords: Allogeneic hematopoietic cell transplantation; Graft-versus-host disease (GvHD); Ibrutinib; Tyrosine-protein kinase BTK inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Chronic Disease
  • Drug Interactions
  • Graft vs Host Disease / drug therapy*
  • Humans
  • Pyrazoles / adverse effects
  • Pyrazoles / metabolism
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / metabolism
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*

Substances

  • Pyrazoles
  • Pyrimidines
  • ibrutinib