JAK1/2 Inhibitor Ruxolitinib for the Treatment of Systemic Chronic Active Epstein-Barr Virus Disease: A Phase II Study

• Ruxolitinib brought out complete response, which is the disappearance of disease activity, in 22.2% (2/9) of sCAEBV patients.

• Ruxolitinib is a potent treatment drug that may improve HSCT outcomes by suppressing disease activity in sCAEBV

Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a rare intractable EBV-positive T-cell or NK-cell lymphoid neoplasm with systemic inflammation. The only curative treatment is allogeneic hematopoietic stem cell transplantation (allo-HSCT). Disease activity defined by multiple inflammatory symptoms is associated with poor survival. In sCAEBV, STAT3 is constitutively activated in EBV-infected T and NK cells and promotes their activation and survival. Ruxolitinib, a Janus kinase 1/2 inhibitor, suppresses the STAT3 activation in vitro, suggesting its clinical potential. We firstly conducted a phase II, multicenter, open-label study to investigate the effects of ruxolitinib on disease activity of sCAEBV. Complete response (CR) and partial response (PR) were defined as complete and partial resolution of disease activity, respectively. Nine patients received ruxolitinib, and seven patients completed the study. The primary endpoint, CR rate (%) 56 days after the administration or at early termination as defined in the protocol, was 22.2% (2/9). No patient showed hematopoietic toxicity nor disease progression. Notably, 71.4% (5/7) of the patients who completed the study were treated at our outpatient clinic. One patient developed a severe adverse event of oral bleeding due to lesion shrinkage during the treatment, and ruxolitinib was discontinued. EBV-DNA levels in whole blood did not change significantly whether the treatment was effective or not. After ruxolitinib treatment, seven patients received allo-HSCT, and five of them achieved CR with undetectable EBV-DNA levels in whole blood. Ruxolitinib is a potent treatment drug that may improve allo-HSCT outcomes by suppressing disease activity of sCAEBV. The trial was registered at UMIN numbered UMIN000035121.