Ruxolitinib-combined doxorubicin-etoposide-methylprednisolone regimen as a salvage therapy for refractory/relapsed haemophagocytic lymphohistiocytosis: a single-arm, multicentre, phase 2 trial

Authors：Wang, Jingshi; Zhang, Rui; Wu, Xiaoyan; Li, Fei; Yang, Haixia; Liu, Ligen; Guo, Haixia; Zhang, Xuejun; Mai, Huirong; Li, Hui; Wang, Zhao^*

Source：British Journal of Haematology, 2021, 193(4): 761-768.

DOI：10.1111/bjh.17331

• haemophagocytic lymphohistiocytosis
• salvage therapy
• ruxolitinib
• multicentre
• clinical trial

We performed a multicentre, non-randomised trial (NCT03533790) to investigate the efficacy of ruxolitinib combined with the doxorubicin-etoposide-methylprednisolone (Ru-DEP) regimen as a salvage therapy for refractory/relapsed haemophagocytic lymphohistiocytosis (HLH). All patients failing to achieve a complete or partial response 2 weeks after initial HLH-94/HLH-04 regimen or relapsed after remission were enrolled in the study between June 2018 and June 2019. The efficacy was evaluated 2 weeks after initiating Ru-DEP salvage therapy. Fifty-four eligible patients with refractory/relapsed (R/R) HLH were enrolled. One case could not be evaluated for efficacy. Excluding 12 patients who had previously received the DEP regimen, the overall response rate was 32 of 41 (78 center dot 0%) patients, with eight of 41 (19 center dot 5%) achieving complete response and 24 of 41 (58 center dot 5%) attaining a partial response. Of the R/R HLH patients who had previously received the DEP regimen, 7 of 12 (58 center dot 3%) achieved a partial response. Ferritin and soluble CD25 concentrations were significantly lower (P < 0 center dot 05), while the platelet count increased significantly (P = 0 center dot 034), and triglycerides decreased significantly (P = 0 center dot 002) compared with those before treatment. The Ru-DEP regimen may be a safe and effective salvage therapy, remaining effective in refractory/relapsed HLH following DEP treatment, especially in macrophage activation syndrome. In addition, the regimen can be considered for patients with contraindications to glucocorticoid, especially those with gastrointestinal bleeding.

• Institution
  河北医科大学; 南昌大学; 华中科技大学; 上海交通大学; 1; 南方医科大学