University of British Columbia
Project Term: July 1, 2022 - June 30, 2025
Our team is the first to develop a polyomic pediatric cGvHD biomarker test for assessing the risk of developing cGvHD. A cooperative adult phase III clinical trial, CTTC1901, between Canada and Australia, focused on decreasing cGvHD (N=350 patients), offers an ideal opportunity to validate adult cGvHD biomarkers. This proposal will utilize the pediatric polyomic approach to validate a cGvHD risk assignment and diagnostic algorithm in adult hematopoietic stem cell transplant (HSCT).
For the foreseeable future, hematopoietic stem cell transplant (HSCT) remains a critical—and sometimes the only—immune-based therapeutic option for patients with high-risk and refractory (resistant to previous therapies) blood cancers. While CAR-T cells are an exciting new immune therapy, ~50% of CAR-T cell-treated patients must still receive HSCT. Moreover, HSCT efficacy has improved with a 2-year, event free survival rate of >80% in a recent large, multinational trial, ensuring its continued usefulness as immune therapy for leukemia. The Canadian national registry estimates that there are >2000 HSCT survivors, of which 70% have had chronic graft-versus-host disease (cGVHD) and >60% have been hospitalized for HSCT-related health issues 2-10 years post-HSCT. Similarly, Australia performs 600 HSCTs a year with 60% complicated by graft-versus-host disease. Our strategy is to increase HSCT safety by focusing on cGvHD as the most significant non-malignant survivorship issue in HSCT. We will accomplish our goals by decreasing the impact of cGvHD, decreasing prolonged immune suppression, and increasing successful social attainment in this population.
By integrating the successful pediatric “Applied Biomarkers in Late Effects of Children and Adolescents (ABLE)” biomarker team approach into the current CTTC and ALLG collaborative clinical trial we have an unprecedented opportunity to launch international research initiatives that can address these critical survivorship issues. We believe this will position Canada and Australia as international leaders to inform HSCT survivorship issues. This is highlighted by 2 recent commentaries in the high impact journal, Blood, discussing how the ABLE Team studies are a model for cGvHD research biomarker studies. We anticipate our current collaborative strategy will significantly accelerate the application of biomarker-driven personalized interventions.
Using the CTTC in collaboration with the ALLG network, we propose to take the highly successful ABLE ‘polyomics’ approach used in children to minimize the severe impact of cGvHD on blood cancer survivorship in adults. The current Canadian/Australasian CTTC-1901 randomized phase III clinical trial will study 350 adult patients and was designed at its inception to collect biological samples to look for biomarkers, with cGvHD clinical assessment based on the 2014 National Institutes of Health diagnostic criteria. The aim is to evaluate and apply the cGvHD ‘early risk’ assignment strategy, discovered through the ABLE study, to adults aged 18 – 60 years at time of transplant. This will allow for future development of preemptive measures to minimize or eliminate the morbidity and mortality of cGvHD before it occurs. We propose to Validate and modify a pediatric cGvHD risk assignment and diagnostic algorithm in a Canadian and Australasian cohort that can be applied for adult HSCT recipients.