P17.08 * RENAL THROMBOTIC MICROANGIOPATHY INDUCED BY BEVACIZUMAB IN HIGH GRADE GLIOMA PATIENTS - ABOUT SIX CASES

Abstract

INTRODUCTION: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) has demonstrated its potential efficacy in glioblastoma (GBM). Prospective trials have been performed to investigate its interest as first line treatment in GBM. With the expanding use of bevacizumab, specific adverse effects have been described. Renal complications are well known (hypertension, proteinuria). Nevertheless, thrombotic microangiopathy (TMA) is rare. No case of TMA induced by bevacizumab in glioma patients has been reported. METHODS: Glioma patients with TMA induced by bevacizumab were retrospectively selected from two french neurooncological centers (Pitie Salpetriere, Nancy). Clinical, biological data and renal biopsy results were recorded. RESULTS: Six patients (median age of 58 years, range 32 to 72 years) with high grade gliomas presented a TMA induced by bevacizumab. TMA was diagnosed after a median of 17 doses of bevacizumab (range 13 to 20). Proteinuria was increased in the six patients (median of 1890 mg of protein per 24 hours, range 1290 to 8090). The platelet count and the haptoglobin were low in three patients. The lactic dehydrogenase was elevated in three patients. The blood pressure level was increased in six patients and required antihypertensive therapy with a median of two antihypertensive drugs (range one to five drugs). Bevacizumab discontinuation allowed decrease of blood pressure and proteinuria in four patients. Two patients developped haemolytic-uraemic syndrom with intravascular haemolysis that required plasmapheresis in one patient. This patient had a low level of ADAMTS 13 activity (50%). Renal biopsy was performed in three cases and confirmed TMA. CONCLUSIONS: No case of TMA associated to bevacizumab treatment has been described in glioma patients. This complication remains rare and the pathophysiology is not clearly understood. Considering the large use of bevacizumab in high grade gliomas, TMA would be more frequent. The strict monitoring of blood pressure and proteinuria is essential in patients with bevacizumab treatment.