LGG-34. Nephrological impact of BRAF inhibitors in a pediatric population of central nervous system tumors: a single institution experience

Abstract

BRAF inhibitors (iBRAF) are under investigations in ongoing clinical trials for pediatric brain tumor treatment. Preliminary data regarding the pediatric population report pyrexia, hematological, dermatological, cardiac, and ophthalmic toxicities among the most common adverse events. Acute kidney injury (AKI), mainly due to tubular interstitial injury, has been reported in the adult population. With our study we want to contribute to a more comprehensive knowledge of the short- and long-term nephrological adverse effects of iBRAF in a pediatric population. We collected and reviewed clinical and laboratory data of all patients treated with iBRAF for pediatric central nervous system tumors at our Institution and available for publication. AKI was monitored through serial creatinine measurements, kidney function with estimated glomerular filtration rate (eGFR) and kidney injury with creatinuria/proteinuria ratio. Tubular injury was evaluated with fractional excretion of sodium, potassium and magnesium and with glycosuria. Moreover, urine was examined to detect presence and morphology of erythrocytes. Eight patients were identified, 3 females; median age at treatment start was 9 years (range 2,75 – 18,75). Six patients with BRAFV600E–mutated pediatric Low-Grade Glioma were treated with Vemurafenib, 1 patient with BRAFV600E-mutated pediatric High-Grade Glioma was treated with Vemurafenib and 1 patient with BRAFV600E-mutated Langerhans Cell Histiocytoses was treated with Dabrafenib. Seven patients were considered for analysis. After a median follow up of 3,83 years (range 2,25 – 6,58) no AKI was reported and all patients but two retained normal eGFR at last follow up. No tubular and glomerular injury laboratory findings were detected, and erythrocytes in the urine resulted always below the upper limit of normality. CONCLUSIONS: iBRAF were not associated with AKI and tubular injury. Nevertheless, some data, namely significative decrease of eGFR in two out of seven patients, warrants further investigations.