Comparison of short-term response and long-term outcomes after initial systemic treatment of chronic graft-versus-host disease.

Clinical trials of chronic graft-versus-host disease (cGVHD) often use early endpoints, such as clinical response at 3 or 6 months, as the primary endpoint instead of measures of long-term treatment success, such as the ability to discontinue immunosuppressive treatment after development of immune tolerance and resolution of active disease. We evaluated the ability of defined overall and organ-specific response categories at 3 and 6 months to predict the subsequent success or failure of primary treatment. The analysis included 116 patients evaluated at 3 months after enrollment and 94 patients evaluated at 6 months after enrollment. Success was defined as withdrawal of systemic treatment after resolution of cGVHD without secondary therapy. Failure was defined as secondary systemic treatment, or death or development of bronchiolitis obliterans during primary treatment. With most definitions, response at 3 months and response at 6 months were not statistically significantly correlated with subsequent success of primary treatment. With some definitions, the absence of response at 6 months had a statistically significant correlation with subsequent failure of primary treatment. These findings suggest that early response to the agents currently used for primary treatment does not necessarily predict subsequent tolerance, an important endpoint in the management of cGVHD. Rigorously defined clinical response is an appropriate primary endpoint for studies of cGVHD, but future clinical trials should provide for extended follow-up to ascertain late outcomes that are not necessarily predictable by evaluation of response before 6 months.