The Chronic Graft-vs.-Host Disease Failure-Free Survival (cGVHD-FFS) index

Abstract In clinical trials of chronic graft-versus-host disease (GVHD), the need to start a new systemic treatment is considered a treatment failure. A composite endpoint called “failure-free survival” (FFS) where events are initiation of a new systemic chronic GVHD treatment, recurrent malignancy, and death, has been suggested as a possible long-term indicator of success. The goal of the current study was to identify changes in chronic GVHD manifestations from baseline to 6-months that could accurately predict subsequent longer term FFS, thereby making it possible to assess outcomes earlier than would otherwise be possible. We used data from two prospective, multi-center, observational studies to develop the cGVHD-FFS index. The cGVHD-FFS index was calculated at 6 months, a typical timepoint for assessment of the primary endpoint of phase II chronic GVHD trials. Subsequent FFS was only 45% within the next 2 years. We found that changes in the scores for the eyes, joint/fascia and mouth ulcers from baseline to 6 months were associated with subsequent FFS, but the prognostic accuracy of these changes was not adequate for use in trials. Biomarker studies might help to identify criteria that improve prediction of long-term clinical outcomes in patients with chronic GVHD.