Endothelial activation and stress index (EASIX) as a biomarker to predict ruxolitinib failure for steroid-refractory acute graft-versus-host disease treatment.

Steroid-refractory acute graft-versus-host disease (SR-aGvHD) remains a significant challenge after haematopoietic cell transplantation (HCT). While ruxolitinib (RUX) has shown efficacy for SR-aGvHD, failure predictors are poorly defined. We assessed 78 patients from six Canadian centres who received RUX for SR-aGvHD. Failure-free survival (FFS) was the primary end-point. Endothelial activation and stress index (EASIX) scores were calculated at defined time points, dichotomized using recursive partitioning. A risk score for RUX failure was developed based on key variables. At RUX initiation, 76% of patients had grade 3-4 aGvHD. The best overall response rate was 75%; 58% experienced RUX failure, while the 6-month FFS was 25.7%. EASIX gradually increased over time even after RUX (p < 0.001). Patients with high EASIX at RUX ≥1.11 had a lower FFS at 6 months (17%) than the patients with low EASIX (54%) (hazard ratio [HR] 2.75 [95%CI 1.23-6.15], p = 0.014). A three-factor RUX failure risk score-gut aGvHD, grade 4 aGvHD and high EASIX at RUX start-stratified patients by 6-month FFS rates: 85.7%, 28.0% and 11.0% for score 0 (n = 28), 1 (n = 25) and ≥2 (n = 34) (HR 2.25[1.42-3.55], p < 0.001). High EASIX can predict the risk of RUX failure in addition to gut aGvHD and grade 4 aGvHD. We propose to add other therapeutic interventions to RUX therapy pre-emptively to high EASIX patients.