Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome, and the overall survival of adult patients is poor. Ruxolitinib, a Janus kinase (JAK) 1/2 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 (the Ru-D regimen) had a high response rate and led to favorable short-term survival outcomes in adult HLH patients. In this prospective phase 2 clinical trial, we propose the Ru-D regimen as a first-line treatment for adults newly diagnosed with HLH with unknown triggers (chictr.org.cn identifier: ChiCTR2100049996). 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 endpoint) 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 lymphoma-associated HLH (LAHS) patients was 5.8 months, and most of these patients had NK/T-cell lymphoma. In contrast, the 2-year OS rate of non-LAHS patients was 75%. The overall response rate (ORR) was 85.7% (24/28)
17.9% (5/28) of patients achieved a complete response (CR) during the Ru-D regimen. Overall, the Ru-D regimen was well tolerated in HLH patients. This study demonstrates the efficacy and safety of the Ru-D regimen in adults newly diagnosed with HLH with unknown triggers and warrants a phase 3 randomized controlled study.