scholarly journals Dual BRAF/MEK blockade restores CNS responses in BRAF-mutant Erdheim–Chester disease patients following BRAF inhibitor monotherapy

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Roei D Mazor ◽  
Ran Weissman ◽  
Judith Luckman ◽  
Liran Domachevsky ◽  
Eli L Diamond ◽  
...  
Keyword(s):  
Disease Progression ◽  
Therapeutic Strategy ◽  
Braf Inhibitor ◽  
Response To Therapy ◽  
Cns Disease ◽  
Erdheim Chester Disease ◽  
Braf Mutant ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Background Erdheim–Chester disease (ECD), a rare inflammatory myeloid neoplasm, is known to be fundamentally reliant on the constitutive activation of the MAPK signaling pathway in the majority of patients. Consequently, inhibition of the V600E-mutant BRAF kinase has proven to be a safe and efficacious long-term therapeutic strategy for BRAF-mutant ECD patients. Nevertheless, in a subset of patients with CNS disease, the efficacy of long-term treatment may diminish, facilitating suboptimal responses or disease progression. Methods We retrospectively describe 3 BRAF-mutant ECD patients whose treatment with Vemurafenib was upgraded to Vemurafenib/Cobimetinib due to either disease progression, insufficient response, or unacceptable toxicity. CNS response to therapy was evaluated using magnetic resonance imaging (MRI) and extra-cranial disease was monitored using 18F-fludeoxyglucose positron emission tomography/computed tomography (PET/CT). Results Three patients with a mean age of 52.6 years were treated with Vemurafenib for a mean duration of 26.6 months (range: 6–52). Monotherapies were upgraded to Vemurafenib/Cobimetinib dual therapy. The combination therapy was administered for a mean duration of 21 months (range: 19–23). All patients exhibited clinical and neurological improvement. Regression of lesions on MRI was noted in 2 patients. Both patients characterized by a PET-avid disease responded to the biological treatment regimen with complete metabolic remissions. Conclusion Dual inhibition of BRAF and downstream MEK may be a safe and effective therapeutic strategy for BRAF-mutant ECD patients for whom BRAF inhibitor therapy proved insufficient and as such appropriate for the long-term management of CNS disease in ECD.

A long-term survival case of Erdheim–Chester disease on maintenance hemodialysis

2022 ◽  
Author(s):  
Ryo Konishi ◽  
Takuya Morinishi ◽  
Koji Takaori ◽  
Yuta Iwamoto ◽  
Makiko Kondo ◽  
...  
Keyword(s):  
Maintenance Hemodialysis ◽  
Term Survival ◽  
Long Term Survival ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease ◽  
Survival Case

scholarly journals BRAF-Mutated Erdheim-Chester Disease: Profound Response to Vemurafenib Visualized With Serial Multimodality Imaging

2020 ◽  
Vol 18 (6) ◽  
pp. 650-655
Author(s):  
Javaughn Corey R. Gray ◽  
Jongho Kim ◽  
Michael Digianvittorio ◽  
Nancy K. Feeley ◽  
Paul J. Scheel ◽  
...  
Keyword(s):  
Multimodality Imaging ◽  
Braf Inhibitor ◽  
Response To Treatment ◽  
Elderly Male ◽  
Multisystem Disease ◽  
Disease Response ◽  
Erdheim Chester Disease ◽  
Middle Aged Adults ◽  
Erdheim Chester ◽  
Chester Disease

Erdheim-Chester disease (ECD) is an extremely rare and aggressive non-Langerhans histiocytic disorder. ECD typically presents with bone pain in middle-aged adults, although some patients present with multisystem disease involving the skeleton, central nervous system, cardiovascular system, lungs, and other disease sites. The etiology of ECD is currently unknown, but it is thought to be a reactive or neoplastic disorder. Recently, mutation of the BRAF gene has been found in >50% of ECD cases, and this gene has become a therapeutic target for patients with ECD. Vemurafenib, a BRAF inhibitor, has been approved by the FDA for treatment of ECD. This report presents an elderly male patient with an aggressive phenotype of ECD and highlights the utility of multimodality imaging in monitoring the clinical course and disease response to treatment with vemurafenib.

scholarly journals Relevant Imaging Presentation of Erdheim-Chester Disease: A case-report

2018 ◽  
Vol 13 (2) ◽  
Author(s):  
Philippe Jacob
Keyword(s):  
Bone Pain ◽  
Clinical Manifestations ◽  
Braf Inhibitor ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Bone Lesions ◽  
Erdheim Chester Disease ◽  
Promising Treatment ◽  
Erdheim Chester ◽  
Chester Disease

Erdheim-Chester disease (ECD) is a rare non-Langerhans multisystemic histiocytosis. This disorder is characterised by CD68+/CDa1- foamy histiocytes infiltration in tissues, especially bones, retroperitoneum, heart, lung and brain. Clinical manifestations may range from asymptomatic bone lesions to multiorganic symptoms. Bone pain in lower extremities are however the most common symptoms. Typical imaging findings include symmetric dyaphyseal osteosclerosis of long bones, periaortic sheathing (“coated aorta”) and retroperitoneal infiltration (“hairy kidney”). Lung and brain radiological abnormalities may also be seen on imaging screening. BRAF-V600E mutation is associated with around half of ECD patients. Vemurafenib, a mutated BRAF inhibitor, is a promising treatment for patients with this mutation. We present the case of a 60 years old man who arrived with a pathological right humerus fracture, and who was first admitted for a tuberculosis suspicion. ECD was first suspected with imaging screening.

scholarly journals Long-term outcome of basilar stenosis in Erdheim–Chester disease

Medicine ◽  
2016 ◽  
Vol 95 (36) ◽  
pp. e4813 ◽  
Author(s):  
Stéphane Mathis ◽  
Gaëlle Godenèche ◽  
Julien Haroche ◽  
Serge Milin ◽  
Adrien Julian ◽  
...  
Keyword(s):  
Term Outcome ◽  
Long Term Outcome ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

scholarly journals Erdheim‐Chester disease progression from miliary pulmonary nodules to large tumours

2019 ◽  
Vol 7 (8) ◽  
Author(s):  
Jun Shiihara ◽  
Hiromitsu Ohta ◽  
Satoshi Ikeda ◽  
Tomohisa Baba ◽  
Koji Okudera ◽  
...  
Keyword(s):  
Disease Progression ◽  
Pulmonary Nodules ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

scholarly journals An unusual Erdheim-Chester disease with orbital involvement: a case report

2016 ◽  
Vol 10 ◽  
Author(s):  
Giuseppe Brunori ◽  
Aurelio Seidita ◽  
Lydia Giannitrapani ◽  
Antonietta Serruto ◽  
Francesco Bencivinni ◽  
...  
Keyword(s):  
Poor Response ◽  
Response To Therapy ◽  
Erdheim Chester Disease ◽  
Left Lateral Ventricle ◽  
Temporal Horn ◽  
History Of ◽  
Total Body ◽  
Erdheim Chester ◽  
Chester Disease ◽  
Maxillary Sinuses

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis with multiorgan involvement and a specific tropism for perivascular and fatty connective tissue, of unclear origin, with poor response to therapy. Its identification is difficult because of the variable clinical presentation and its lack of knowledge. We report the case of a 63-years-old woman, with a history of bilateral orbital pseudotumor, who comes to our attention because of progressively worsening asthenia, vomiting and systemic inflammation. Total body computerized tomography scan showed a volumetric increase of choroid plexus of the temporal horn of the left lateral ventricle, presence of solid retrobulbar tissue at the level of both maxillary sinuses, lung fibrosis, and retroperitoneal and peri-aortic infiltration. The association of these signs addressed to a diagnosis of Erdheim- Chester disease. Thus, although extremely rare, the diagnosis of Erdheim-Chester disease must be considered in the case of bilateral retro-orbital tumors and multisystemic involvement.

Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAFV600E-Mutated Erdheim-Chester Disease

2015 ◽  
Vol 33 (5) ◽  
pp. 411-418 ◽  
Author(s):  
Julien Haroche ◽  
Fleur Cohen-Aubart ◽  
Jean-François Emile ◽  
Philippe Maksud ◽  
Aurélie Drier ◽  
...  
Keyword(s):  
Evaluation Criteria ◽  
Braf Inhibitor ◽  
Standardized Uptake Value ◽  
Sustained Efficacy ◽  
Erdheim Chester Disease ◽  
Positron Emission ◽  
Surface Measurements ◽  
Magnetic Resonance Imaging Mri ◽  
Erdheim Chester ◽  
Chester Disease

Purpose Histiocytoses are rare disorders with heterogeneous prognosis. BRAFV600E mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. Patients and Methods Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAFV600E mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). Results All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. Conclusion Vemurafenib has an objective and sustained efficacy in BRAFV600E-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.

Treatment of Erdheim-Chester Disease with Long-Term High-Dose Interferon-α

2012 ◽  
Vol 41 (6) ◽  
pp. 907-913 ◽  
Author(s):  
Baptiste Hervier ◽  
Laurent Arnaud ◽  
Frederic Charlotte ◽  
Bertrand Wechsler ◽  
Jean Charles Piette ◽  
...  
Keyword(s):  
Interferon Α ◽  
High Dose ◽  
Erdheim Chester Disease ◽  
High Dose Interferon ◽  
Erdheim Chester ◽  
Chester Disease
Sign in / Sign up

Export Citation Format

Share Document