Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD

Abstract Background Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD (‘ocGVHD’), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. Methods We performed a secondary analysis of data from the ABA2 trial, in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Results The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX + placebo and CNI/MTX + abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. Conclusion ocGVHD is associated with increased cGVHD severity scores, both at presentation and at maximum disease severity. OcGVHD was also associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype.