Individualized everolimus treatment for tuberous sclerosis-related angiomyolipoma promotes treatment adherence and response

Abstract

Background: Everolimus is a potential alternative to embolization and nephrectomy for managing tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML). In 2016, National Health Service England approved its use through regional centres for renal AML ≥30 mm showing interval growth. Evidence of lesion stabilization or reduction after 6 months is mandated for continuation of long-term treatment.

Methods: From November 2016 to June 2021, all potentially eligible adult TSC patients with AML across Yorkshire and Humber were referred for assessment and monitoring. Eligible patients underwent baseline renal magnetic resonance imaging (MRI) assessment and a follow-up MRI scan after 6 months on everolimus. Dose titration was guided by trough levels and lesion responsiveness using a new 3D MRI volumetric protocol.

Results: Of 28 patients commencing treatment, 19 tolerated everolimus for >3 months. Overall, 11 patients (40%) discontinued treatment, mostly due to recurrent infections (42%) and allergic reactions (25%). Sixty-eight percent required dose adjustments from the initiating dose (10 mg) due to sub-optimal trough levels (38%), minimal AML response (15%) or adverse events (47%). 3D volumetric assessment confirmed a reduction in AML volume of a pre-selected index lesion in all treatment-naïve cases (n = 14), showing superiority over 2D measurements of lesion diameter.

Conclusion: In this cohort, everolimus promoted AML regression in all patients who tolerated the drug for >6 months with stabilization observed over 3 years. Trough levels enabled individual dose titration to maximize responsiveness and minimize side effects. The use of 3D MRI assessment of lesion volume was superior to 2D measurements of lesion diameter in monitoring treatment response.

Keywords: angiomyolipoma; everolimus; monitoring; safety; treatment outcome; tuberous sclerosis complex.

Graphical Abstract

FIGURE 1:

Map of referrals of TS patients with AML to Sheffield from across and outside the Yorkshire and Humber region between 2016 and 2021. The size of the circles is proportional to the numbers of patients referred per million population.

FIGURE 2:

Flowchart summarizing 37 TS patients referred for assessment of eligibility for everolimus initiation and their outcomes over 55 months. LFT, liver function test.

FIGURE 3:

Age and renal function (eGFR) of patients on everolimus for >3 months at their baseline assessment visit.

FIGURE 4:

Percentage change in target AML volume over treatment course for patients on everolimus for >6 months with available baseline and serial MRI scans (n = 14).