An endpoint associated with clinical benefit after initial treatment of chronic graft-versus-host disease

Blood. 2017 Jul 20;130(3):360-367. doi: 10.1182/blood-2017-03-775767. Epub 2017 May 11.

Abstract

No gold standard has been established as a primary endpoint in trials of initial treatment of chronic graft-versus-host disease (GVHD), and evidence showing the association of any proposed primary endpoint with clinical benefit has not been conclusively demonstrated. To address this gap, we analyzed outcomes in a cohort of 328 patients enrolled in a prospective, multicenter, observational study within 3 months after diagnosis of chronic GVHD. Complete and partial response, stable disease, and progressive disease were defined according to the 2014 National Institutes of Health Consensus Development Conference on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease. Success was defined as complete or partial response with no secondary systemic treatment or recurrent malignancy at 1 year after enrollment. Success was observed in fewer than 20% of the patients. The burden of disease manifestations at 1 year was lower for patients in this category than for those with stable or progressive disease. Systemic treatment ended earlier, and subsequent mortality was lower among patients with complete or partial response than among those with stable or progressive disease and those who had received secondary systemic treatment. We conclude that survival with a complete or partial response and no previous secondary systemic treatment or recurrent malignancy at 1 year after initial systemic therapy is associated with clinical benefit, a critical characteristic for consideration as a primary endpoint in a pivotal clinical trial. This prospective observational study was registered at www.clinicaltrials.gov as #NCT00637689.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Calcineurin Inhibitors / therapeutic use
  • Chronic Disease
  • Disease Progression
  • Endpoint Determination*
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Photopheresis
  • Prednisone / therapeutic use
  • Prospective Studies
  • Recurrence
  • Rituximab / therapeutic use
  • Severity of Illness Index
  • Sirolimus / therapeutic use
  • Survival Analysis
  • Transplantation Conditioning
  • Transplantation, Homologous
  • United States

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Rituximab
  • Prednisone
  • Sirolimus

Associated data

  • ClinicalTrials.gov/NCT00637689