Ixazomib decreases the risk of chronic graft-versus-host disease: identification of cGVHD biomarkers

Chronic graft-versus-host disease (cGVHD) is the leading cause of long-term morbidity and mortality after allogeneic hematopoietic stem cell transplantation. We hypothesize that it is possible to decrease its risk by manipulating the immune response in late phases of transplantation. We performed a prospective randomized trial including 73 patients. Patients in the treatment arm received 4 mg of ixazomib (IXZ) every 28 days from day +100. With a median follow-up of 24 months, the cumulative incidence of moderate/severe cGVHD in the IXZ vs control groups at 1 and 2 years were: 3.23% vs 30.2% (hazard ratio [HR], 0.089; P = .02) and 13% vs 43% (HR, 0.23; P = .01), respectively. Estimates for cGVHD and relapse-free survival at 2 years were 81% for IXZ and 49% for the control group (HR, 0.30). Increased STAT3 and p38 phosphorylation in T cells, and higher proportion of B cells that have undergone immunoglobulin isotype switching and circulating plasma cells on day +180 were associated with a significantly higher risk of developing moderate/severe cGVHD. The administration of IXZ decreases the risk of moderate/severe cGVHD. It is possible to identify biological patterns by flow cytometry to predict the risk of cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT03225417.