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

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.

© 2017 by The American Society of Hematology.

Figures

Figure 1.

Flow of outcomes among patients enrolled in the study within 3 months after beginning systemic treatment of chronic GVHD. Patients who received second-line systemic treatment before enrollment in the study were excluded from this analysis. Fifteen of the 32 patients with relapse died within the first year after enrollment. CR/PR indicates complete or partial response at the time of assessment; SD/PD indicates stable or progressive disease at the time of assessment. *This category includes patients who were alive without recurrent or progressive malignancy at 1 year but did not have the intended assessment.

Figure 2.

Patients with a CR or PR at the 1-year landmark and no secondary systemic treatment before the 1-year landmark have a shorter time to end of systemic treatment and better subsequent survival than do those with stable disease or progression at the landmark or secondary systemic treatment before the landmark. (A) Cumulative incidence of ended systemic treatment. (B) Survival after the 1-year landmark. CR/PR indicates complete or partial response at the time of assessment (n = 39). SD/PD indicates stable or progressive disease at the time of assessment (n = 59). New Rx indicates patients who received secondary systemic treatment of chronic GVHD before the landmark (n = 104). A few patients ended systemic treatment before the landmark. IST, immunosuppressive treatment.