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

Summary 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.