Dr Paczesny on ST2 as a Biomarker for Acute GVHD Risk Post-Transplant

"When we measured ST2 [levels] at day 14, we [could] accurately see that the area under the curve of 0.74 or [higher]…predicted [whether patients] would have a risk of developing aGVHD by day 56 or death by day 100."

Sophie Paczesny MD, PhD, a professor in the Department of Microbiology and Immunology and co-leader of the Cancer Immunology Program at the Hollings Cancer Center at the Medical University of South Carolina, discussed findings from a prospective, observational study evaluating ST2 as a risk/susceptibility biomarker for the development of acute graft-vs-host disease (aGVHD) or death following hematopoietic cell transplantation (HCT).

Prior retrospective data have validated interleukin (IL) 1 receptor-like 1, which encodes the IL-33 decoy receptor ST2, as a predictive biomarker of resistance to aGVHD therapy and as a prognostic biomarker of nonrelapse mortality (NRM). However, its prospective qualification as a risk biomarker—defined as a measurable indicator present prior to disease onset—for grades 2 to 4 aGVHD by day 56 or death by day 100 post-HCT had not been previously established.

Findings from this multisite study of 160 patients, presented during the 51st Annual EBMT Meeting, showed that ST2 levels of 60 ng/mL or greater measured at day 14 post-HCT were identified as a significant risk biomarker for grades 2 to 4 aGVHD, as well as for NRM, Paczesny explained. The analysis included patients receiving either calcineurin inhibitor (CNI)–based or posttransplant cyclophosphamide (PTCy)–based GVHD prophylaxis; approximately two-thirds of patients received CNI, and approximately one-third of patients received PTCy, according to Paczesny. ST2 levels were measured at both day 14 and day 17 post-HCT; however, day 14 levels provided slightly greater predictive accuracy and were thus the focus of further analysis, Paczesny noted.

The area under the curve for ST2 level exceeded 0.74 in both prophylaxis cohorts, demonstrating the ability of ST2 to stratify patients at risk for developing grades 2 to 4 aGVHD by day 56 or dying by day 100, Paczesny said. ST2 [measurement] also accurately predicted NRM but was not associated with relapse or infection rates, consistent with its role as a biomarker specific to GVHD and NRM, Paczesny added. Additionally, elevated ST2 levels at day 14 were predictive of subsequent moderate-to-severe chronic GVHD, indicating the potential of early post-HCT ST2 measurement to forecast outcomes as late as 6 months after transplant, Paczesny concluded.