Systemic vasculitis associated with vemurafenib treatment

Mirouse, Adrien; Savey, Léa; Domont, Fanny; Comarmond, Cloé; Barète, Stéphane; Plaisier, Emmanuelle; Rouvier, Philippe; Cacoub, Patrice; Saadoun, David

doi:10.1097/md.0000000000004988

Cited by 11 publications

(7 citation statements)

References 18 publications

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“…Vasculitis is mainly described in single patients treated with BRAFi as cutaneous side effects in the context of panniculitis,45 50–53 and as leukocytoclastic vasculitis,45 54 but also involving the kidney as glomerulonephritis55 56 and the eye as retinal vasculitis 57…”

Section: Methodsmentioning

confidence: 99%

Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management

Heinzerling¹,

et al. 2019

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The inhibition of the mitogen-activated protein kinases signalling pathway through combined use of BRAF and MEK inhibitors (BRAFi+MEKi) represents an established therapeutic option in patients with BRAF-mutated, advanced melanoma. These efficient therapies are well tolerated with mostly moderate and reversible side effects and a discontinuation rate due to adverse events of 11.5%–15.7%. Median duration of therapy ranges between 8.8 and 11.7 months. Based on data from confirmatory trials, safety profiles of three BRAFi+MEKi combinations were reviewed, that is, dabrafenib plus trametinib, vemurafenib plus cobimetinib and encorafenib plus binimetinib. Many adverse events are class effects, such as cutaneous, gastrointestinal, ocular, cardiac and musculoskeletal events; some adverse events are substance associated. Fever (dabrafenib) and photosensitivity (vemurafenib) are the most common and clinically prominent examples. Other adverse events are less frequent and the association to one substance is less strong such as anaemia, facial paresis (encorafenib), neutropenia (dabrafenib), skin rash, QTc prolongation and increased liver function tests (vemurafenib). This narrative review provides recommendations for monitoring, adverse event evaluation and management focusing on the clinically relevant side effects of the three regimens.

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Section: Methodsmentioning

confidence: 99%

Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management

Heinzerling¹,

et al. 2019

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“…10,11 Severe cutaneous side effects can occur with BRAF inhibitor therapy, such as squamous cell carcinoma and vasculitis; interferon α may be better tolerated. 11,13,14 Longitudinal follow-up is needed with this treatment. In Quebec, vemurafenib therapy costs 136,56$CAD/day and is also used for metastatic melanoma.…”

Section: Discussionmentioning

confidence: 99%

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

P¹

2018

Can Journ Gen Int Med

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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.

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“…We found only 1 case similar to ours. Mirouse et al [ 8 ] described the case of a 75-year-old man with a history of Erdheim–Chester disease, treated with vemurafenib. Two years after treatment he was hospitalized for diffusive edema with acute kidney injury.…”

Section: Discussionmentioning

confidence: 99%

“…Renal function recovered completely after cyclophosphamide and high-dose steroid treatment. Mirouse et al [ 8 ] also reviewed all the cases reporting vasculitis while using vemurafenib and found 5 other cases. All these cases presented cutaneous effects of vemurafenib, with skin vasculitis.…”

Section: Discussionmentioning

confidence: 99%

Glomerulonephritis and granulomatous vasculitis in kidney as a complication of the use of BRAF and MEK inhibitors in the treatment of metastatic melanoma

et al. 2017

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Rationale:BRAF and MEK inhibitors have significantly improved the prognosis of metastatic melanoma, by inhibiting both the mitogen-activated protein kinase (MAP-kinase) pathway. They are associated with infrequent adverse kidney events. Most of these are related to the use of BRAF inhibitors and involve interstitial nephritis with acute tubular necrosis.Patient concerns:We report a unique case of glomerulonephritis with renal granulomatous vasculitis in a patient diagnosed with metastatic melanoma treated with BRAF and MEK inhibitors. The patient was a 55-year old woman, who presented a melanoma of the right thigh with pulmonary metastasis. Treatment started in November 2015, with Encorafenib and Binimetinib, new BRAF and MEK inhibitors, respectively. Two months after the beginning of the treatment, there was a worsening of her renal function with significant proteinuria.Diagnoses:Kidney biopsy showed extracapillary proliferation in the glomeruli with a granulomatous reaction.Interventions and outcomes:Renal function recovered completely after withdrawal of the chemotherapy.Lessons:All the reported kidney adverse events secondary to BRAF and MEK inhibitors in the literature are related to the use of BRAF inhibitors. Some previous reported mechanistic investigations also provide insight between BRAF inhibitors and podocytes injuries. Therefore, encorafenib most likely is the main responsible of the disease. However, evidence has emerged that inhibition of the MAP kinase pathway could also enhance autoimmunity. Thus, binimetinib may also have played a role and the combination of BRAF and MEK inhibitors may have facilitated this autoimmune kidney disease.

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Systemic vasculitis associated with vemurafenib treatment

Cited by 11 publications

References 18 publications

Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management

Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management

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

Glomerulonephritis and granulomatous vasculitis in kidney as a complication of the use of BRAF and MEK inhibitors in the treatment of metastatic melanoma

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