Ruxolitinib combined with dexamethasone for adult patients with newly diagnosed hemophagocytic lymphohistiocytosis in China
De Zhou, Xianbo Huang, Lixia Zhu, Xuelian Hu, Xiudi Yang, Mixue Xie, Xin Huang, Fang Yu, Juying Wei, Liya Ma, Jingjing Zhu, Shuqi Zhao, Wanzhuo Xie, Hongyan Tong, Jie Jin, Xiujin Ye
Abstract
ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome, and the overall survival (OS) of adult patients is poor. Ruxolitinib, a Janus kinase 1/2 (JAK1/2) inhibitor, has shown promise in treating HLH and exerts synergistic effects when combined with dexamethasone. Our pilot study preliminarily demonstrated that the combination of ruxolitinib and dexamethasone (Ru-D regimen) had a high response rate and led to favorable short-term survival outcomes in adult patients with HLH. In this prospective phase 2 clinical trial, we propose the Ru-D regimen as a first-line treatment for adults newly diagnosed as having HLH with unknown triggers. A total of 28 Chinese patients were enrolled, and the median follow-up time was 25.1 months (range, 0.87-34.0). The 2-month OS rate (the primary end point) was 85.7%, which exceeded our expected 2-month OS rate of 75%. The 6-month and 2-year OS rates were 67.9% (19/28) and 53.6% (15/28), respectively. The median OS of patients with lymphoma-associated HLH (LAHS) was 5.8 months, and most of these patients had natural killer/T-cell lymphoma. In contrast, the 2-year OS rate of patients without LAHS was 75%. The overall response rate was 85.7% (24/28); of 28 patients, 5 (17.9%) achieved a complete response during the Ru-D regimen. Overall, the Ru-D regimen was well tolerated in patients with HLH. This study demonstrates the efficacy and safety of the Ru-D regimen in adults newly diagnosed as having HLH with unknown triggers and warrants a phase 3 randomized controlled study. This trial was registered at www.chictr.org.cn as #ChiCTR2100049996).