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).
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