Sirolimus plus prednisone for Erdheim-Chester disease: An open-label trial

Davide Gianfreda, Maria Nicastro, Maricla Galetti, Federico Alberici, Domenico Corradi, Gabriella Becchi, Giorgio Baldari, Massimo De Filippo, Stefania Ferretti, Gabriella Moroni, Rosario Foti, Marcella Di Gangi, Guido Jeannin, Raphael Saffroy, Jean François Emile, Carlo Buzio, Augusto Vaglio

Research output: Contribution to journalArticlepeer-review


Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, to whose pathogenesis neoplastic and immune-mediated mechanisms contribute. Mammalian target of rapamycin (mTOR)-inhibitors have antiproliferative and immunosuppressive properties. We tested in this study, the efficacy and safety of the mTOR-inhibitor sirolimus (SRL) plus prednisone (PDN) in patients with ECD. PDN was given initially at 0.75 mg/kg per day, tapered to 5 to 2.5 mg per day by month 6. Target SRL blood levels were 8 to 12 ng/mL. Treatment was continued for at least 24 months in patients who showed disease stabilization or improvement. Ten patients were enrolled; 8 achieved stable disease or objective responses, whereas 2 had disease progression. Responses were mainly observed at the following sites: retroperitoneum in 5/8 patients (62.5%), cardiovascular in 3/4 (75%), bone in 3/9 (33.3%), and central nervous system (CNS) in 1/3 (33.3%). The median follow-up was 29 months (interquartile range, 16.5-74.5); 2 patients died of progressive CNS disease and small-cell lung cancer, respectively. Treatment-related toxicity was mild. Using immunohistochemistry and immunofluorescence on ECD biopsies, we detected expression in foamy histiocytes of the phosphorylated forms of mTOR and of its downstream kinase p70S6K, which indicated mTOR pathway activation. In conclusion, SRL and PDN often induce objective responses or disease stabilization and may represent a valid treatment of ECD. The trial is registered at the Australia-New Zealand Clinical Trial Registry as #ACTRN12613001321730.

Original languageEnglish
Pages (from-to)1163-1171
Number of pages9
Issue number10
Publication statusPublished - Sep 3 2015

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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