Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With <i>BRAF<sup>V600E</sup></i>-Mutated Erdheim-Chester Disease

Haroche, Julien; Cohen‐Aubart, Fleur; Émile, Jean-François; Maksud, Philippe; Drier, Aurélie; Tolédano, Dan; Barète, Stéphane; Charlotte, Frédéric; Cluzel, Philippe; Donadieu, Jean; Benameur, Neïla; Greniér, Philippe; Besnard, Sophie; Ory, J. P.; Lifermann, François; Idbaïh, Ahmed; Granel, B.; Graffin, B.; Hervier, B.; Arnaud, Laurent; Amoura, Zahir

doi:10.1200/jco.2014.57.1950

Cited by 247 publications

(206 citation statements)

References 33 publications

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“…No existen estudios controlados, sólo unos pocos ensayos observacionales prospectivos 1,21 . En algunas series de casos comunicados en el siglo XX se emplearon corticoides, alcaloides de la vinka, antraciclinas, ciclofosfamida, metotrexato, cladribina, bifosfonatos y trasplante autólogo de células troncales, sin obtener curación 3,8 .…”

Section: Discussionunclassified

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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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Section: Discussionunclassified

“…L a enfermedad de Erdheim-Chester (EEC) es una variedad rara de histiocitosis, habiéndo-se comunicado alrededor de 500 casos 1 . Frecuentemente existe compromiso cardiovascular, que puede ser asintomático y detectarse en RM y/o scanner [2][3][4] .…”

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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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“…For CNS involvement, location (supra-and infra-tentorial) and changes in size of parenchymal lesions were evaluated using T2-weighted images at MRI. 16,17 Repeated biopsies to evaluate histologic or cellular changes induced by treatment were not performed. Changes in quality of life were assessed with the 36-Item Short Form Health Survey (SF-36) questionnaire, administered by healthcare workers during monthly re-evaluations.…”

Section: Clinical and Radiological Criteria Of Response To Therapymentioning

confidence: 99%

“…Changes in target lesions were evaluated by comparing baseline and post-treatment PET/ CT images, by means of a side-by-side image analysis to evaluate dimensional as well as FDG uptake changes. 7,16 Similarly, follow-up cardiac and cerebral MRIs were compared to baseline images, and lesion size was measured before treatment and during follow-up evaluations. Coated aorta, pericardial effusion, and pseudotumoral atrial infiltration were measured at the first and last visits.…”

Section: Clinical and Radiological Criteria Of Response To Therapymentioning

confidence: 99%

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Tocilizumab in patients with multisystem Erdheim–Chester disease

et al. 2017

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Treatment of Erdheim-Chester disease (ECD), a rare non-Langerhans histiocytosis, relies on interferon-a, chemotherapeutic agents such as purine analogs, cytokine-blocking agents and BRAF inhibitors. Since interleukin (IL)-6 levels are elevated in serum and lesions of ECD patients, we evaluated the therapeutic efficacy and safety of IL-6 blockade with tocilizumab. We conducted an open-label, single-arm, phase II, prospective study of tocilizumab in three patients with multisystem ECD and poor tolerance/contraindications to IFN-a. Modifications of symptoms attributed to ECD represented the criteria for evaluation of clinical response. Changes at positron emission tomography scan, computed tomography scan, and magnetic resonance imaging at month 6 represented the main criteria for the evaluation of radiological response.Sustained complete clinical response and partial radiological improvement were observed in two patients, paralleled by modulation of systemic pro-inflammatory mediators. In spite of disease stabilization or improvement at extra-neurological sites, a third patient experienced a radiologic and clinical progression of central nervous system involvement, mirrored by a dramatic increase of circulating IL-6 and related cytokines. These findings indicate that IL-6 inhibition can be effective in ECD, but caution is advisable in patients with neurologic involvement. IL-6 emerges as a central mediator in ECD pathogenesis.

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Vemurafenib for BRAF V600–Mutant Erdheim-Chester Disease and Langerhans Cell Histiocytosis

et al. 2018

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IMPORTANCE The histiocytic neoplasms Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are highly enriched for BRAF V600 mutations and have been previously shown to be responsive to treatment with vemurafenib, an inhibitor of the BRAF V600 kinase. However, the long-term efficacy and safety of prolonged vemurafenib use in these patients are not defined. Here we analyze the final efficacy and safety data for vemurafenib in patients with ECD and LCH enrolled in the VE-BASKET study. OBJECTIVE To determine the efficacy and safety of vemurafenib in adults with ECD or LCH enrolled in the VE-BASKET study. DESIGN, SETTING, AND PARTICIPANTS The VE-BASKET study was an open-label, nonrandomized, multicohort study for patients with nonmelanoma cancers harboring the BRAF V600 mutation. Patients with BRAF V600–mutant ECD or LCH were enrolled in an “other solid tumor” cohort of the VE-BASKET study, and they were enrolled in the present study. INTERVENTIONS Patients received vemurafenib, 960mg, twice daily continuously until disease progression, study withdrawal, or occurrence of intolerable adverse effects. MAIN OUTCOMES AND MEASURES The primary end point was confirmed objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Secondary end points included progression-free survival (PFS), overall survival (OS), metabolic response by modified positron-emission tomography (PET) Response Criteria in Solid Tumors (PERCIST) using 18F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT), and safety. RESULTS A total of 26 patients from the VE-BASKET trial (22 with ECD, 4 with LCH) were included in the present study (14 women and 12 men; median age, 61 years; age range, 51–74 years). The confirmed ORR was 61.5%(95%CI, 40.6%–79.8%) in the overall cohort and 54.5%(95%CI, 32.2%–75.6%) in patients with ECD. All evaluable patients achieved stable disease or better. The median PFS and OS had not been reached in the overall cohort at study closure despite a median follow-up of 28.8 months; 2-year PFS was 86%(95%CI, 72%–100%), and 2-year OS was 96%(95%CI, 87%–100%). All 15 patients evaluated by FDG-PET/CT achieved ametabolic response, including 12 patients (80%) with a complete metabolic response. The most common adverse events (AEs) in the overall cohort included arthralgia, maculopapular rash, fatigue, alopecia, prolonged QT interval, skin papilloma, and hyperkeratosis. Hypertension and dermatologic AEs occurred at higher rates than those reported in metastatic melanoma. CONCLUSIONS AND RELEVANCE In this study, vemurafenib had prolonged efficacy in patients with BRAF V600–mutant ECD and LCH and warrants consideration as a new standard of care for these patients.

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Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAF^V600E-Mutated Erdheim-Chester Disease

Abstract: Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.

Cited by 247 publications

References 33 publications

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

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

Tocilizumab in patients with multisystem Erdheim–Chester disease

Vemurafenib for BRAF V600–Mutant Erdheim-Chester Disease and Langerhans Cell Histiocytosis

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

Abstract: Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.

Cited by 247 publications

References 33 publications

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

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

Tocilizumab in patients with multisystem Erdheim–Chester disease

Vemurafenib for BRAF V600–Mutant Erdheim-Chester Disease and Langerhans Cell Histiocytosis

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Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAF^V600E-Mutated Erdheim-Chester Disease