{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:43:32Z","timestamp":1792244612478,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Erdheim\u2013Chester disease (ECD) is a rare histiocytic neoplasm characterized by heterogeneous clinical manifestations and limited evidence to guide targeted therapy. While MEK inhibitors (MEKi) are increasingly used, data on their real\u2010world efficacy, durability, and safety remain incomplete. We analyzed outcomes of patients with ECD treated with MEKi monotherapy across eight countries and assessed the dynamics and predictors of response, treatment retention, and the safety profile of MEKi. We included 170 patients and were able to evaluate response in 159 (94%) of them. Objective responses were observed in 112 patients (70%), disease stabilization in 35 (22%), and disease progression in 12 (8%). Response rates were independent of treatment lines and underlying molecular alterations. The median time to best response was 14 months, with an estimated 2\u2010year probability of response of 61% (95% CI 51%\u201367%). In multivariable analysis, dyslipidemia (odds ratio [OR] 0.359, 95% CI 0.171\u20130.745) and neurodegeneration (OR 0.354, 95% CI 0.144\u20130.864) were associated with a lower probability of response to MEKi, while cutaneous and gastrointestinal involvement with a higher probability. After a median follow\u2010up of 27 months (interquartile range [IQR] 12\u201357), the treatment retention rate was 76%, with most discontinuations attributable to toxicity. Adverse events were reported in 106 patients (62%) and were severe in 39 patients (23%). The estimated 2\u2010year event\u2010free survival was 65% (95% CI 57%\u201372%), and the estimated 2\u2010year overall survival was 80% (95% CI 72%\u201386%). MEKi monotherapy provides robust and durable clinical efficacy in patients with ECD, with high response rates and favorable long\u2010term outcomes, despite a substantial burden of toxicity.<\/jats:p>","DOI":"10.1002\/hem3.70499","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:55:34Z","timestamp":1791298534000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MEK inhibition achieves robust and durable responses in Erdheim\u2013Chester disease"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4954-5744","authenticated-orcid":false,"given":"Francesco","family":"Pegoraro","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence Florence Italy"},{"name":"Department of Hematology and Oncology Meyer Children's Hospital IRCCS Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9licien","family":"Triboulet","sequence":"additional","affiliation":[{"name":"Internal Medicine Department 2 Institut E3M, French Reference Centre for Histiocytosis, Piti\u00e9\u2010Salp\u0207tri\u00e8re Hospital, CIMI INSERM\u2010UMRS 1135, Sorbonne University, Assistance Publique\u2010H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3389-9473","authenticated-orcid":false,"given":"Matthias","family":"Papo","sequence":"additional","affiliation":[{"name":"Internal Medicine Department 2 Institut E3M, French Reference Centre for Histiocytosis, Piti\u00e9\u2010Salp\u0207tri\u00e8re Hospital, CIMI INSERM\u2010UMRS 1135, Sorbonne University, Assistance Publique\u2010H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-1952","authenticated-orcid":false,"given":"Francesco","family":"Peyronel","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0827-3051","authenticated-orcid":false,"given":"Anita","family":"Argentieri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Meyer Children's Hospital IRCCS Florence Italy"},{"name":"Clinical Pediatrics, Department of Molecular Medicine and Development University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Razanamahery","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology Dijon University Hospital Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-1204","authenticated-orcid":false,"given":"Ahmed","family":"Idbaih","sequence":"additional","affiliation":[{"name":"Neuro\u2010Oncology Department Sorbonne University, Paris Brain Institute \u2010 ICM, Inserm, CNRS, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, DMU Neurosciences, Assistance Publique\u2010H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-3357","authenticated-orcid":false,"given":"Polyzois","family":"Makras","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes and LCH and ECD Adult Clinic 251 Hellenic Air Force &amp; VA General Hospital Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4463-7647","authenticated-orcid":false,"given":"Ofer","family":"Shpilberg","sequence":"additional","affiliation":[{"name":"Adelson School of Medicine Ariel University Ariel Israel"},{"name":"Institute of Hematology, Assuta Medical Centers Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4685-0679","authenticated-orcid":false,"given":"Oshrat","family":"Hershkovitz\u2010Rokah","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Faculty of Natural Sciences Ariel University Ariel Israel"},{"name":"Translational Research Lab Assuta Medical Centers Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3270-411X","authenticated-orcid":false,"given":"Michael","family":"Girschikofsky","sequence":"additional","affiliation":[{"name":"Division of Hematology With Stem Cell Transplantation, Hemostaseology and Medical Oncology, Department of Internal Medicine I Ordensklinikum Linz Elisabethinen Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6585-9586","authenticated-orcid":false,"given":"Matthew","family":"Collin","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences Newcastle University Newcastle Upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Bowles","sequence":"additional","affiliation":[{"name":"Norwich Medical School University of East Anglia Norwich United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyen H.","family":"Gohil","sequence":"additional","affiliation":[{"name":"Deparment of Hematology University College London Hospitals NHS Foundation Trust London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6691-9210","authenticated-orcid":false,"given":"Rodothea","family":"Amerikanou","sequence":"additional","affiliation":[{"name":"Deparment of Hematology University College London Hospitals NHS Foundation Trust London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3925-9541","authenticated-orcid":false,"given":"Emmanuel","family":"Ledoult","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Lille University Hospital Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9816-8572","authenticated-orcid":false,"given":"Tanguy","family":"Le Scornet","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Nantes University Hospital Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"de Menthon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology Bicetre Hospital, Assistance Publique \u2010 H\u00f4pitaux de Paris Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0254-3394","authenticated-orcid":false,"given":"Etienne","family":"Riviere","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Haut\u2010L\u00e9v\u00e8que University Hospital Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1621-4308","authenticated-orcid":false,"given":"Xavier","family":"Boulu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Amiens University Medical Center Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Dupuy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Ramsay Sant\u00e9 Clinique Aguil\u00e9ra Biarritz France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille","family":"Aouba","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Caen University Hospital Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-0927","authenticated-orcid":false,"given":"Stanislas","family":"Faguer","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Organ Transplantation National Referral Centre for Rare Kidney Diseases\u2010SORARE, Toulouse University Hospital Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2572-2187","authenticated-orcid":false,"given":"Xavier","family":"Solanich","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Bellvige University Hospital, Hospitalet de Llobregat Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6192-9812","authenticated-orcid":false,"given":"Elena","family":"Sieni","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Meyer Children's Hospital IRCCS Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1593-9750","authenticated-orcid":false,"given":"St\u00e9phane","family":"Barete","sequence":"additional","affiliation":[{"name":"Unit of Dermatology Piti\u00e9\u2010Salp\u0207tri\u00e8re Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris Sorbonne University Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Bellino","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allegy and Rare Diseases San Raffaele Hospital IRCCS Vita\u2010Salute San Raffaele University Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5440-2078","authenticated-orcid":false,"given":"Alessandro","family":"Tomelleri","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allegy and Rare Diseases San Raffaele Hospital IRCCS Vita\u2010Salute San Raffaele University Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-3794","authenticated-orcid":false,"given":"Corrado","family":"Campochiaro","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allegy and Rare Diseases San Raffaele Hospital IRCCS Vita\u2010Salute San Raffaele University Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7428-315X","authenticated-orcid":false,"given":"Lorenzo","family":"Dagna","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allegy and Rare Diseases San Raffaele Hospital IRCCS Vita\u2010Salute San Raffaele University Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahir","family":"Amoura","sequence":"additional","affiliation":[{"name":"Internal Medicine Department 2 Institut E3M, French Reference Centre for Histiocytosis, Piti\u00e9\u2010Salp\u0207tri\u00e8re Hospital, CIMI INSERM\u2010UMRS 1135, Sorbonne University, Assistance Publique\u2010H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6073-4466","authenticated-orcid":false,"given":"Jean\u2010Fran\u00e7ois","family":"Emile","sequence":"additional","affiliation":[{"name":"EA4340 BECCOH, Versailles SQY University, Pathology Department, Ambroise Par\u00e9 Hospital Assistance Publique\u2010H\u00f4pitaux de Paris Boulogne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fleur","family":"Cohen\u2010Aubart","sequence":"additional","affiliation":[{"name":"Internal Medicine Department 2 Institut E3M, French Reference Centre for Histiocytosis, Piti\u00e9\u2010Salp\u0207tri\u00e8re Hospital, CIMI INSERM\u2010UMRS 1135, Sorbonne University, Assistance Publique\u2010H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Vaglio","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Experimental and Clinical Sciences \u201cMario Serio\u201d University of Florence Florence Italy"},{"name":"Nephrology Unit Meyer Children's Hospital IRCCS Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9794-1316","authenticated-orcid":false,"given":"Julien","family":"Haroche","sequence":"additional","affiliation":[{"name":"Internal Medicine Department 2 Institut E3M, French Reference Centre for Histiocytosis, Piti\u00e9\u2010Salp\u0207tri\u00e8re Hospital, CIMI INSERM\u2010UMRS 1135, Sorbonne University, Assistance Publique\u2010H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0944-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002766"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003507"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-025-02656-w"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.1950"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-771873"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1012-y"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-025-02614-6"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024028032"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.70137"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.108.057307"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004478"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023020569"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102658"},{"key":"e_1_2_10_18_1","unstructured":"National Cancer Institute. Patient\u2010Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO\u2010CTCAE).https:\/\/healthcaredelivery.cancer.gov\/pro\u2010ctcae"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000145368.17934.91"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-199605000-00005"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022009013"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-025-02526-5"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab107"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hem3.70392"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2025.02.007"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24696"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.70026"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac741"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.09.027"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaf023"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024015399"}],"container-title":["HemaSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.70499","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hem3.70499","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.70499","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:18:24Z","timestamp":1792243104000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hem3.70499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/hem3.70499"],"URL":"https:\/\/doi.org\/10.1002\/hem3.70499","archive":["Portico"],"relation":{},"ISSN":["2572-9241","2572-9241"],"issn-type":[{"value":"2572-9241","type":"print"},{"value":"2572-9241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70499"}}