Abstract
Objective: To assess the safety and efficacy of low-dose everolimus maintenance therapy for tuberous sclerosis complex-related renal angiomyolipoma (TSC-RAML) patients that had previously undergone standard-dose treatment for a minimum of 6 months.Materials and Methods: In total, 24 patients with a definitive TSC diagnosis were enrolled from April 2018 – April 2019 at Xiangya Hospital, Central South University. All patients underwent low-dose everolimus maintenance therapy following standard-dose everolimus induction therapy for a minimum of 6 months. Patients additionally underwent TSC1/TSC2 genetic testing, And they were followed-up at 3, 6, 12, 18, and 24 months. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria were used to monitor patient RAML responses, while adverse events (AEs) were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). P < 0.05 was the significance level for all analyses, which were performed using SPSS 19.0.Results: TSC1/TSC2 gene mutations were present in all 24 patients, all of whom achieved a significant reduction in TSC-RAML volume within the initial 6-month induction therapy period, and exhibited volume stabilization during the low-dose maintenance therapy treatment period without any instances of TSC-RAML regrowth. Adverse events (AEs) were significantly less severe and less frequent over the course of maintenance therapy relative to standard therapy.Conclusions: Low-dose everolimus maintenance therapy represents an effective approach to achieving TSC-RAML control following a minimum of 6 months of full-dose induction therapy, and may be associated with decreases in everolimus-related AE frequency and severity.
Highlights
Tuberous sclerosis complex (TSC) is an autosomaldominant syndrome that impacts between 1 in 6,000 and 1 in 10,000 individuals, resulting in characteristic neurodevelopmental features and the development of multiple tumors in organs including the skin, heart, lungs, brain, and kidneys [1]
Everolimus is an mammalian target of rapamycin (mTOR) inhibitor that has shown promise for the treatment of complications associated with TSC including renal angiomyolipoma (RAML), seizures, facial angiofibromas, and subependymal giant cell astrocytomas (SEGAs) [6,7,8,9]
20 and 4 were found to harbor TSC2 and TSC1 mutations, respectively, via next-generation sequencing (NGS) (Table 2). Three of these patients had a history of epilepsy, two were treated with antiepileptic monotherapy, while the remaining one with antiepileptic combination therapy. Five of these patients were diagnosed with lymphangioleiomyomatosis (LAM), all suffered from skin lesions, and one presented with SEGAs
Summary
Tuberous sclerosis complex (TSC) is an autosomaldominant syndrome that impacts between 1 in 6,000 and 1 in 10,000 individuals, resulting in characteristic neurodevelopmental features and the development of multiple tumors in organs including the skin, heart, lungs, brain, and kidneys [1]. Upwards of 80% of TSC patients are affected by renal angiomyolipoma (RAML) [2], which is characterized by multiple bilateral lesions in the smooth muscles, adipose tissue, and vasculature [3]. As these tumors typically grow over time, TSC-RAML can result in arterial hypertension and imposes a risk of life-threatening hemorrhage, which is the leading cause of TSC-associated mortality among adults with this condition [4]. The International Tuberous Sclerosis Complex Consensus Conference held in 2012 recommended the first-line use of mTOR inhibitors for the treatment of RAML ≥ 3 cm in diameter, even when not associated with any clinical symptoms [10]
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