{"title":"JAK1/2 inhibitor ruxolitinib for the treatment of systemic chronic active Epstein-Barr virus disease: a phase 2 study","authors":"Yu Uemura , Masahide Yamamoto , Masataka Ishimura , Hirokazu Kanegane , Akihisa Sawada , Akihiro Hirakawa , Ken-Ichi Imadome , Mayumi Yoshimori , Masashi Nagata , Kouhei Yamamoto , Norio Shimizu , Ryuji Koike , Ayako Arai","doi":"10.1016/j.bneo.2024.100053","DOIUrl":null,"url":null,"abstract":"<div><h3>Abstract</h3><div>Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a rare intractable EBV-positive T-cell or natural killer (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, signal transducer and activator of transcription 3 (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 conducted a phase 2, multicenter, open-label study to investigate the effects of ruxolitinib on disease activity of sCAEBV. Complete response (CR) and partial response were defined as complete and partial resolution of disease activity, respectively. Nine patients received ruxolitinib, and 7 patients completed the study. The primary end point, 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 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, 7 patients received allo-HSCT, and 5 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 University hospital Medical Information Network (UMIN), numbered UMIN000035121.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 1","pages":"Article 100053"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Neoplasia","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2950328024000530","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a rare intractable EBV-positive T-cell or natural killer (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, signal transducer and activator of transcription 3 (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 conducted a phase 2, multicenter, open-label study to investigate the effects of ruxolitinib on disease activity of sCAEBV. Complete response (CR) and partial response were defined as complete and partial resolution of disease activity, respectively. Nine patients received ruxolitinib, and 7 patients completed the study. The primary end point, 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 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, 7 patients received allo-HSCT, and 5 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 University hospital Medical Information Network (UMIN), numbered UMIN000035121.
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