Rationale and efficacy of interleukin-1 targeting in Erdheim–Chester disease

Aouba, Achille; Georgin‐Lavialle, Sophie; Pagnoux, Christian; Silva, Nicolas Martin; Renand, Amédée; Galateau-Salle, Françoise; Toquin, Sophie Le; Bensadoun, H.; Larousserie, Frédérique; Silvera, S.; Provost, Nicole; Candon, Sophie; Séror, Raphaèle; Menthon, Mathilde de; Hermine, Olivier; Guillevin, Loı̈c; Bienvenu, Boris

doi:10.1182/blood-2010-04-279240

Cited by 128 publications

(109 citation statements)

References 44 publications

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“…Recently, treatments blocking the proinflammatory pathway of interleukin (IL)-1 or the RAS/RAF/MEK/ERK tumorigenic mutational network provided efficacy in refractory ECD [3,4]. However, several concerns persist with these drugs, including partial efficacy more often with anakinra, poor tolerance and unacceptable side effects with vemurafenib, considering, moreover, that targetable mutations are detected only in less than 60% of ECD biopsies.…”

Section: Letter To the Editormentioning

confidence: 99%

Superior efficacy and tolerance of reduced doses of vemurafenib plus anakinra in Erdheim-Chester disease: Towards the paradigm of combined targeting and immune therapies

Franconieri¹,

Silva²,

Boysson³

et al. 2016

Acta Oncologica

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Section: Letter To the Editormentioning

confidence: 99%

Superior efficacy and tolerance of reduced doses of vemurafenib plus anakinra in Erdheim-Chester disease: Towards the paradigm of combined targeting and immune therapies

Franconieri¹,

Silva²,

Boysson³

et al. 2016

Acta Oncologica

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“…The treatment of two ECD patients (neither with cardiovascular or CNS involvement) with recombinant human interleukin-1 receptor (anakinra) was described at this time, and seemed to be promising [47]. We therefore treated ten ECD patients at our institution with anakinra: overall, the efficacy was poor.…”

Section: Assessing Disease Activitymentioning

confidence: 99%

“…Dagna et al studied both spontaneous and stimulated cytokine production by mononuclear cells in biopsy fragments from a single patient [58]: tumor necrosis factor α was produced after stimulation, and IL-6 and IL-8 were secreted spontaneously, with IL-8 acting as a chemoattractant for polymorphonuclear cells and monocytes. Aouba et al reported evidence from two patients indicating that targeting the IL-1 pathway might be beneficial [47]. We recently assayed serum samples from 37 ECD patients for 23 cytokines [59••], and found high IFNα, IL-1/IL1-RA, IL-6, IL-12, and MCP-1 titers, indicating strong and systemic immune activation.…”

Section: Pathophysiologymentioning

confidence: 99%

Erdheim–Chester Disease

et al. 2014

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Erdheim-Chester disease (ECD) is a rare (approximately 500 known cases worldwide), non-inherited, nonLangerhans form of histiocytosis of unknown origin, first described in 1930. It is characterized by xanthomatous or xanthogranulomatous infiltration of tissues by foamy histiocytes, "lipid-laden" macrophages, or histiocytes, surrounded by fibrosis. Diagnosis of ECD involves the analysis of histiocytes in tissue biopsies: these are typically foamy and CD68+ CD1a− in ECD, whereas in Langerhans cell histiocytosis (LCH) they are CD68+ CD1a+. 99 Technetium bone scintigraphy revealing nearly constant tracer uptake by the long bones is highly suggestive of ECD, and a "hairy kidney" appearance on abdominal CT scan is observed in approximately half of ECD cases. Central nervous system involvement is a strong prognostic factor and an independent predictor of death in cases of ECD. Optimum initial therapy for ECD seems to be administration of interferon α (or pegylated interferon α), and prolonged treatment significantly improves survival; however, tolerance may be poor. Cases of ECD present with strong systemic immune activation, involving IFNα, IL-1/IL1-RA, IL-6, IL-12, and MCP-1, consistent with the systemic immune Th-1-oriented disturbance associated with the disease. More than half of ECD patients carry the BRAF V600E mutation, an activating mutation of the protooncogene BRAF. A small number of patients harboring this mutation and with severe multisystemic and refractory ECD have been treated with vemurafenib, a BRAF inhibitor, which was proved very beneficial.

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“…La dosis empleada es 1-2 mg/kg/día por vía subcutánea. Los efectos secundarios más frecuentes son cefalea, artralgias, nasofaringitis, prurito y eritema cutáneo 3,15,16 .…”

Section: Discussionunclassified

“…En ellos se han ensayado drogas antineoplásicas, biológicas e inmunosupresoras 3,7,[10][11][12][13][14][15][16][17][18][19][20][21] .…”

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Tratamiento con sirolimus y prednisona en enfermedad de Erdheim-Chester con compromiso cardiaco: Caso clínico

Vega

Santamarina

2016

Rev. méd. Chile

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Rationale and efficacy of interleukin-1 targeting in Erdheim–Chester disease

Cited by 128 publications

References 44 publications

Superior efficacy and tolerance of reduced doses of vemurafenib plus anakinra in Erdheim-Chester disease: Towards the paradigm of combined targeting and immune therapies

Superior efficacy and tolerance of reduced doses of vemurafenib plus anakinra in Erdheim-Chester disease: Towards the paradigm of combined targeting and immune therapies

Erdheim–Chester Disease

Tratamiento con sirolimus y prednisona en enfermedad de Erdheim-Chester con compromiso cardiaco: Caso clínico

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