Ixazomib decreases the risk of chronic graft-versus-host disease: identification of cGvHD biomarkers. Open Access

• Ixazomib, an oral proteasome inhibition, prevents the development of moderate/severe cGvHD.

• Patterns of immune system on T and B cells studied by flow cytometry predict the development of cGvHD.

Chronic graft-versus-host disease (cGvHD) is the leading cause of long-term morbi-mortality after allogeneic transplantation (allo-HSCT). 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%, HR=0.089, p=0.02 and 13% vs 43% HR=0.23, p=0.01, respectively. Estimates for cGvHD and relapse free survival (GRFS) at 2 years were 81% for IXZ and 49% for control group, HR = 0.30. Increased STAT3 and p38 phosphorylation in T cells, 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 Ixazomib decreases the risk of moderate/severe cGvHD. It is possible to identify biological patterns by flow cytometry to predict the risk of cGvHD. ClinicalTrials.gov Identifier: NCT03225417