Treatment-Sensitive and Treatment-Dependent Chronic Graft-versus-Host Disease Yield Superior Failure-Free and Overall Survival Compared to Treatment-Resistant Chronic Graft-versus-Host Disease

Response to chronic graft-versus-host disease (cGVHD) treatment may help predict prognosis and outcomes. We hypothesized that cGVHD response to treatment and ability to taper immunosuppression defines distinct treatment response categories that differ in risk factors and prognosis. Our aim was to determine specific clinical characteristics and outcomes associated with 3 distinct cGVHD treatment response groups based on response and duration of immune suppression therapy (IST) as: treatment sensitive (TS), resistant (TR) and treatment dependent (TD) cGVHD. This is a retrospective single-institution cohort study including 1142 consecutive adult and pediatric allogeneic hematopoietic cell transplant (HCT) recipients for malignant and non-malignant disorders at the University of Minnesota (2008-2016). All donor, graft, conditioning regimens, and GVHD prophylaxis strategies were included while only patients who commenced systemic treatment within 30 days of diagnosis of cGVHD were included. A total of 185 patients developed cGVHD requiring IST within 30 days of cGVHD diagnosis are included in this analysis. At 1 year after cGVHD onset, 13% were TS, 27% TD, and 60% TR (including 14% deceased), while at 2 years, 29% were TS, 5% TD, and 66% TR (22% deceased). From a landmark analysis starting 1 year after cGVHD onset, 5-year failure free survival (FFS) and OS were lowest in the TR (FFS 38% and OS 70%), with comparable outcomes in the TD (74% and 82%) and TS (79% each) groups, respectively. Compared to those with no cGVHD, TR cGVHD was associated with worse OS at 5 years after cGVHD (HR 2.09 vs. no cGVHD; 95% CI, 1.3-3.3; P < 0.01). Our findings suggest that refining cGVHD classifications into three treatment response states defines important predictors of early and late clinical outcomes and identifies those needing more effective treatments.