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Master Thesis

Description des atteintes rénales associées aux inhibiteurs de BRAF et de MEK utilisés dans la prise en charge thérapeutique du mélanome

Abstract : Background: anti-BRAF and anti-MEK therapies have significantly improved overall and specific survival of BRAFV600 mutant melanoma. With the large use of these treatments, cases of renal toxicity have been increasingly reported over the last ten years. Our objective was to characterize the prevalence, risk factors and clinical features of acute kidney injury associated with targeted therapies. Methods: We performed a retrospective monocentric cohort study in the University Hospital of Bordeaux studying the kidney outcomes of patients who underwent an anti-BRAF and anti-MEK therapy for a metastatic melanoma between January 2013 and December 2020. The primary outcome was the occurrence of targeted therapy-associated acute kidney injury (TT-AKI), defined as a 1.5-fold increase from baseline in serum creatinine, according to the KDIGO Guidelines. AKI severity and etiology was determined for each case through chart review. Results: 281 patients received targeted therapy for a metastatic melanoma. Twelve patients developed an AKI associated with the targeted therapy. Independent risk factors for AKI were treatment with angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers. Three kidney biopsies were performed: one patient treated with encorafenib and binimetinib had typical lesion of acute interstitial nephritis resolved with corticosteroids. 112 renal adverse event reports were recorded in the national adverse event reporting system between January 2013 and March 2021. 67 % of the adverse events were reported in male patients. Acute kidney injury was the most common adverse renal event, reported in 74 (66.1%) patients. Only 4 (3.6%) electrolyte disorders were reported, included Fanconi syndrome and hypernatremia. Conclusions: knowledge of AKI associated with anti-BRAF and anti-MEK therapy is essential. TT-AKI can lead to treatment discontinuation and to CKD. In the future, the growing use of TT may increase the incidence of TTAKI with a long-term impact on the development of CKD in these patients.
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Submitted on : Monday, October 4, 2021 - 1:35:22 PM
Last modification on : Tuesday, October 26, 2021 - 3:21:51 AM
Long-term archiving on: : Wednesday, January 5, 2022 - 6:33:00 PM


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  • HAL Id : dumas-03364053, version 1



Marine Novion. Description des atteintes rénales associées aux inhibiteurs de BRAF et de MEK utilisés dans la prise en charge thérapeutique du mélanome. Sciences du Vivant [q-bio]. 2021. ⟨dumas-03364053⟩



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