Clinical and disease characteristics of initial participants at time of enrollment in THRIVE, a prospective, observational cohort study of patients at risk for chronic graft‑versus‑host disease

Abstract

Abstract Background: Chronic graft-versus-host disease (cGVHD) is a leading cause of non-relapse mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Further investigation is needed to understand cGVHD risk, diagnostic features, and outcomes. Patient-reported outcomes (PROs) are important for characterizing the direct and indirect impact of cGVHD on patients, caregivers, and the healthcare system. THRIVE (NCT05919511) is a prospective, longitudinal observational study of patients at risk for cGVHD to describe the clinical course, burden, and practice patterns for cGVHD. THRIVE uses a novel app-based platform designed for rigorous collection of PROs related to symptoms, quality of life, and indirect costs to the healthcare system. We report preliminary patient demographics and clinical characteristics at study enrollment. Methods: THRIVE includes adults aged ≥18 years in the United States who were enrolled 90–180 days after allo-HCT. Follow-up is for 36 months at intervals determined by clinician standard practice; a virtual site is available for patients who return to community sites for follow-up. Presence or absence of GVHD symptoms, cGVHD therapies when applicable, and adverse events are captured in medical records at clinical visits every ~3 months. In all, 13 PROs are assessed (Cutaneous GVHD Questionnaire [CuGQ], General Anxiety Disorder [GAD-7], Lee Total Symptom Scale [TSS; 7-day], modified Frenchay Activities Index [mFAI], modified Patient-Generated Subjective Global Assessment [mPG-SGA], Oral Health Impact Profile [OHIP-14], Ocular Surface Disease Index [OSDI-12], Patient Health Questionnaire [PHQ-9], Patient-Reported Baseline Data [PRBD], Patient-Reported Caregiver Assessment [PRCA], Patient-Reported Economic, Income, and Insurance Data [PREIID], Patient-Reported Outcomes Measurement Information System–Sexual Function [PROMIS-SF], and Pulmonary GVHD Questionnaire [PulmGQ]). Patients are randomized to sequence groups to complete rotating sets of 4–5 PRO measures via digital platform, monthly (Year 1) then every 2 months (Years 2–3). Recruitment is ongoing (target, 1500 patients). Results: This interim report includes the first 340 patients enrolled in THRIVE (data cutoff: June 17, 2025) at 22 sites across the United States since August 1, 2023. Median (range) age was 60.5 (19–83) years (>70 years, n=60 [18%]). Most patients were male (n=190, 56%), White (n=276, 81%), and had college/graduate education (n=219, 64%). Underlying disease was malignant in 328 (96%) patients; most common malignancies requiring allo-HCT were acute myeloid leukemia (n=129, 38%), myelodysplastic syndrome (n=50, 15%), and acute lymphocytic leukemia (n=37, 11%). Most patients (n=212, 62%) were in complete remission at time of allo-HCT, 282 (83%) enrolled after their first allo-HCT, and median (range) time from allo-HCT to enrollment was 111 (77–211) days. Transplant source was most commonly peripheral blood stem cells (n=272, 80%) from unrelated (n=229, 67%) donors, of whom 169 (50%) were male. Overall, 188 (55%) patients had human leukocyte antigen identical HCT, 72 (21%) had mismatched HCT, and 55 (16%) had haploidentical HCT. Conditioning regimens were myeloablative for 177 (34%) patients, reduced intensity for 164 (48%), and non-myeloablative for 16 (5%). At data cutoff, 296 (87%) patients were continuing in THRIVE; 18/44 (41%) patients who discontinued were alive at discontinuation. There were 107 patients (31%) who developed acute GVHD before enrollment (grade I, n=52; grade II, n=35; grade III, n=9; grade IV, n=0; missing/unknown, n=11); 85 (79%) received systemic treatment for acute GVHD. Overall, 28 (8%) patients had cGVHD at enrollment (mild, n=25; moderate/severe, n=3). Organs affected by cGVHD were skin (n=13), eyes (n=4), and gastrointestinal tract (n=3). Conclusions: THRIVE aims to report on clinical practice for managing risk and treatment of cGVHD after allo-HCT in a prospective cohort of ~1500 patients in the United States for ≤3 years. Although real-world assessment of PROs can be associated with challenges including willingness to participate in an observational study and the collection of data without routine clinical visits, the virtual hybrid design is intended to improve patient access and facilitate data collection. In the 22 months since initiation, 340 patients have been enrolled at 22 sites, and the discontinuation rate is low.