Discordant treatment response between clinicians and patients with skin chronic GVHD and association with mortality

Summary: Abstract Body: Both clinician-reported and patient-reported treatment response (CRTR and PRTR) are critical measures of therapeutic efficacy in skin chronic GVHD (cGVHD), however, these outcomes are not always correlated. Identifying factors associated with discordant treatment response between clinicians and patients and comparing the association of CRTR and PRTR with mortality will assist in integration of objective and subjective endpoints in clinical trials and practice. In this multicenter cohort study of adults with skin cGVHD, we identified patient and disease characteristics associated with discordance between CRTR and PRTR, defined as ≥1-point difference on a 3-point scale (improved, stable, worse). The association of CRTR and PRTR with nonrelapse mortality and their prognostic values were assessed. Of 489 adults with skin cGVHD (n=192 [39%] female, median age 55 years [IQR:43-62]), n=321 (66%) had concordance and n=168 (34%) discordance between CRTR and PRTR. Patients with sclerotic cGVHD had greater odds of discordant treatment response in both directions compared to those without sclerosis (adjusted OR (aOR) 2.33 [CI:1.21-4.51, p=0.012] PRTR better than CRTR and aOR 3.42 [CI:1.53-7.65, p=0.003] CRTR better than PRTR). Both CRTR (aHR 2.27 [CI:1.46-3.54, p<0.001]) and PRTR (aHR 1.87 [CI:1.13-3.09, p=0.014]) were associated with nonrelapse mortality in patients with skin cGVHD. In the subset with sclerosis, only PRTR was associated with nonrelapse mortality (aHR 2.13 [CI:1.05-4.30, p=0.036]) and had the highest concordance measure with mortality (Harrell’s C: 0.77). Patients with sclerosis are more likely to have discordance between CRTR and PRTR, with PRTR associated and prognostic of mortality. Both CRTR and PRTR should be reported in skin cGVHD clinical trials with endpoint priority dependent on study design and treatment goal. Varshini Babu¹, Daniel Shin¹, Stephanie J. Lee², Lynn Onstad², Alison W. Loren³, Joel M. Gelfand¹, Emily Baumrin¹ 1. Dermatology, University of Pennsylvania, Philadelphia, PA, United States. 2. Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA, United States. 3. Medicine, University of Pennsylvania, Philadelphia, PA, United States. Clinical Research: Epidemiology and Observational Research