Ixazomib as chronic GvHD prophylaxis: Findings from a phase II trial

Chronic graft-versus-host disease (cGvHD) is the leading cause of long-term morbidity and mortality post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although biomarkers have been described for risk of acute graft-versus-host disease, few have been identified to predict cGvHD and none are utilized extensively in clinical transplant settings.

A prospective, randomized phase II trial (NCT03225417) in 73 patients evaluated delayed administration of ixazomib (n = 39) vs control (n = 34) as moderate/severe cGvHD prophylaxis in patients post-allo-HSCT (Day +100) and aimed to identify novel biomarkers of cGvHD. 

Results, including the primary endpoint of incidence of moderate/severe cGvHD at 12 months, were published in Blood Advances by Caballero-Velázquez et al.¹

Key learnings

Patients who received ixazomib had a reduced cumulative incidence of moderate/severe cGvHD compared with control at 1 year (3.23% vs 30.2%; HR, 0.089; p = 0.039) and 2 years (13% vs 43%; HR, 0.23; p = 0.052). 

Ixazomib was associated with a 2-year GRFS benefit vs control (81% vs 49%; HR, 0.30; p = 0.004), with a trend towards a lower incidence of relapse (27% vs 13.6%; p = 0.22).  

At Day +180, elevated STAT3 and p38 phosphorylation in T cells, higher B-cell class switching, BAFF receptor expression, and circulating plasma cells were associated with a higher risk of moderate/severe cGvHD, supporting their potential as biomarkers of cGvHD. 

These findings support the administration of ixazomib in the late phase of allo-HSCT to reduce incidence of cGvHD, and biomarkers were identified that may predict cGvHD risk.