Etanercept in Steroid-Refractory Acute Graft Versus Host Disease: Clinical Response, Toxicity, and Long-Term Outcomes

Steroid refractory acute graft versus host disease (SR-aGVHD) is seen in 30%-40% of patients undergoing allogeneic hematopoietic stem cell transplant (allo HSCT). We report our experience with etanercept (ETA) as a first-line treatment for SR-aGVHD during a period when ruxolitinib was not available in India. We retrospectively analysed 43 allo HSCT patients from 2010 to 2019 who received ETA for SR-aGVHD. The primary objective was to assess the overall response rate with etanercept. Secondary objectives included overall survival (OS), organ specific responses, causes of mortality and identification of factors associated with survival and see its utility in the current ruxolitinib era. The response rates (overall response rate [ORR] - complete response [CR] + very good partial response [VGPR] + partial response [PR]) at Day 28 was 69%. The organ-specific ORR was 70% (lower gut), 67% (skin), and 50% (liver). The median OS of responders at Day 28 from ETA start was 6.8 months versus 2.8 months in non-responders (p=0.0008). Patients in whom a reduction in the systemic steroid dose of ≥ 30% by Day 28 from ETA start was possible had a significantly longer median OS (9.5 months versus 3.5 months; p=0.0001). In multivariate analysis, steroid dose reduction of ≥ 30% by Day 28 of the start of ETA was a significant factor for survival (p=0.015). The cause of death in the majority was infection (90%). ETA, used as a second-line agent, has shown an acceptable ORR for SR-aGVHD in our cohort. Despite the good response rates, the group had a high transplantation-related mortality. Infections were the major cause of mortality, and early tapering of systemic steroids may be the key to improving outcomes. In the current ruxolitinib era, etanercept may hold a place in patients where ruxolitinib has failed or is not feasible.