Irreproducibility of GVHD-Predicting Biomarkers Lead to Treatment Failure

Insufficient risk-stratifying graft-versus-host disease (GVHD) biomarkers may lead to failure of prophylactic therapy, according to a study presented at the 2021 TCT Meetings of ASTCT & CIBMTR Digital Experience.

In this prospective, phase II, open-label, single-center study, researchers assessed preemptive therapy of GVHD in patients undergoing hematopoietic cell transplantation (HCT) between 2014 and 2016.

The researchers noted that patients with sIL2Rα >4,500 ng/L or IL15 <31 ng/L on day seven were administered a treatment regimen of anti-thymocyte globulin (ATG, thymoglobulin, 3 mg/kg) the subsequent day. The study comprised a total of 68 patients and 143 controls who did not participate in the study but agreed to have day seven sIL2Rα and IL15 levels determined.

According to the researchers, the study was halted due to a trend toward a lower overall survival (OS) of the “high risk” cohort (day seven sIL2Rα >4,500 ng/L or IL15 <31 ng/L), and these patients received the day eight ATG, compared with the “high risk” controls, who did not receive the day eight ATG. The investigators further noted that the adverse trend in OS was not due to the failure of ATG, but rather a failure of the biomarkers, which was evident by a similar significant GVHD incidence in controls with sIL2Rα >4,500 ng/L or IL15 <31 ng/L versus those with sIL2Rα ≤4,500 ng/L and IL15 ≥31 ng/L.

“The lack of reproducibility of risk-stratifying biomarkers can lead to a failure of preemptive therapy. Multiple validations of biomarkers are needed before proceeding to preemptive therapy trials,” the researchers concluded.

Read more at: https://tct.confex.com/tct/2021/meetingapp.cgi/Paper/16376

Khanolkar RA, et al. Failure of Pre-Emptive Graft-Vs-Host Disease (GVHD) Therapy Due to Irreproducibility of Gvhd-Predicting Biomarkers. Published for the 2021 TCT Meetings of ASTCT & CIBMTR Digital Experience; February 8-12, 2021.