Ruxolitinib combined with doxorubicin, etoposide, and dexamethasone for the treatment of the lymphoma-associated hemophagocytic syndrome

J Cancer Res Clin Oncol. 2020 Nov;146(11):3063-3074. doi: 10.1007/s00432-020-03301-y. Epub 2020 Jul 2.

Abstract

Purpose: Case reports suggest that ruxolitinib-containing treatment could increase the clinical response rate of patients with hemophagocytic syndrome (HPS). This study aimed to explore the effect of ruxolitinib-containing treatment for patients with lymphoma-associated hemophagocytic syndrome (LAHS).

Methods: This was a retrospective study of patients with LAHS hospitalized at the First Affiliated Hospital of Guangdong Pharmaceutical University between October 2017 and September 2019. Patients were treated with HLH-94 (etoposide and dexamethasone) or R-DED regimen (ruxolitinib, doxorubicin, etoposide, and dexamethasone). The clinical characteristics, treatment responses, and overall survival (OS) were compared. The patients were divided into the HLH-94 group (n = 34) and the R-DED group (n = 36).

Results: Compared with HLH-94, R-DED might effectively improve the clinical manifestations, including fever and splenomegaly in patients with LAHS, and control the systemic cytokine storm. The response rate at 2 weeks was 54.8% in the HLH-94 group, which was lower than in the R-DED group (83.3%) (p = 0.011). The OS was significantly prolonged in the R-DED group compared with the HLH-94 group (median, 5 vs. 1.5 months, p = 0.003). The multivariable analysis showed that lower IL-10 levels [hazard ratio (HR)] = 1.000, [95% confidence interval (CI)] 1.000-1.000, p = 0.012), R-DED regimen (HR = 0.196, 95% CI 0.084-0.457, p < 0.001), and non-NK/T-cell lymphoma (HR = 0.254, 95% CI 0.102-0.628, p = 0.003) were associated with better OS. The prognosis of patients with LAHS was generally poor.

Conclusion: Ruxolitinib can be combined with chemotherapy in HPS. It is feasible, with no early signals of increased toxicity.

Keywords: Hemophagocytic syndrome; Lymphoma; Prognosis; Ruxolitinib.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dexamethasone / administration & dosage
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Lymphohistiocytosis, Hemophagocytic / etiology*
  • Lymphoma / complications*
  • Lymphoma / drug therapy*
  • Male
  • Middle Aged
  • Nitriles
  • Pyrazoles / administration & dosage
  • Pyrimidines
  • Retrospective Studies

Substances

  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • Etoposide
  • Dexamethasone
  • Doxorubicin
  • ruxolitinib