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

Abstract

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 (78·0%) patients, with eight of 41 (19·5%) achieving complete response and 24 of 41 (58·5%) attaining a partial response. Of the R/R HLH patients who had previously received the DEP regimen, 7 of 12 (58·3%) achieved a partial response. Ferritin and soluble CD25 concentrations were significantly lower (P < 0·05), while the platelet count increased significantly (P = 0·034), and triglycerides decreased significantly (P = 0·002) 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.

• Authors: Jingshi Wang, Rui Zhang, Xiaoyan Wu, Fei Li, Haixia Yang, Ligen Liu, Haixia Guo, Xuejun Zhang, Huirong Mai, Hui Li, Zhao Wang
• Journal: British journal of haematology (Br J Haematol) Vol. 193 Issue 4 Pg. 761-768 (05 2021) ISSN: 1365-2141 [Electronic] England
• PMID: 33559893 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 British Society for Haematology and John Wiley & Sons Ltd.

Chemical References

• Nitriles
• Pyrazoles
• Pyrimidines
• Etoposide
• Doxorubicin
• ruxolitinib
• Methylprednisolone

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Child
• Child, Preschool
• Doxorubicin (administration & dosage, adverse effects)
• Etoposide (administration & dosage, adverse effects)
• Female
• Humans
• Infant
• Lymphohistiocytosis, Hemophagocytic (blood, drug therapy, mortality)
• Male
• Methylprednisolone (administration & dosage, adverse effects)
• Middle Aged
• Nitriles
• Pyrazoles (administration & dosage, adverse effects)
• Pyrimidines
• Salvage Therapy