1 - Serviço de Pediatria do Hospital Vila Franca de Xira
2 - Centro Hospitalar Barreiro Montijo
3 - Centro Hospitalar Médio Tejo
4 - Serviço de nefrologia, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, EPE
5 - Centro Hospitalar Lisboa Ocidental, EPE
- Reunião da Sociedade Portuguesa de Nefrologia Pediátrica, apresentaçãoo sob a forma de comunicação oral
Introduction: Tuberous sclerosis (TS) is an autosomal dominant disorder characterized by the development of hamartomas in multiple organs due to increased mTOR activity. Everolimus is an mTOR inhibitor that has been approved for the treatment of renal angiomyolipomas (AML) in adult patients. In paediatric patients, everolimus is used off-label for the treatment of AML. This off-label use is based on a post-hoc analysis of the EXIST-1 trial of everolimus for the treatment of subependymal giant cell astrocytomas, which showed an AML volume reduction in paediatric patients. Continued monitoring of real world clinical data on the efficacy and safety of everolimus for the treatment of AML in paediatric patients is needed.
Objective: We aimed to evaluate the efficacy and safety of everolimus for the treatment of AML in paediatric patients with TS, at six months of follow-up.
Material and methods: Longitudinal analysis of a case-series.
Results: We evaluated four patients (one boy and three girls) with AML and genetically confirmed TS, who have completed at least 6 months of treatment with everolimus. All patients had TSC2 mutations, two of whom had TSC2/PKD1 contiguous gene syndrome. The median age at treatment initiation was 17.0 years (range 12.0-19.0; interquartile range (IQR) 14.0;18.5). The median AML longest axis before treatment by magnetic resonance imaging was 5.40 cm (IQR 4.65;6.55). At six months of follow-up, the median reduction in the AML longest axis was 39.7% (median reduction -1.50 cm; IQR -1.85;-0.15). The observed adverse events were dyslipidaemia (4/4), stomatitis (3/4), and acne (1/4). None of these adverse events required withholding the drug.
Conclusions: Our results suggest that everolimus may be effective and safe for the treatment of AML in paediatric patients with TS. Larger studies with long-term follow-up are required to assess whether these results are confirmed.
Keywords: angiomyolipoma, child, everolimus, tuberous sclerosis