Accelerated Cardiac Rhabdomyoma Regression with Everolimus in Infants with Tuberous Sclerosis Complex

Tuberous sclerosis complex is associated with benign tumors such as cardiac rhabdomyomas (RHM) caused by the disinhibition of the mammalian target of rapamycin (mTOR) protein. Recent reports on everolimus, an mTOR inhibitor, have shown size reduction of RHM. We compared cases recently treated with everolimus to historic controls whose first echocardiography was within first month of life. The largest dimension of the largest RHM was reported as a percentage compared to the earliest echocardiography study. Treatment of the four cases was started at a median age of 6.5 days (range 2-20) with an initial enteral dose of 0.1 mg daily, aiming at a therapeutic serum trough level of 5-15 ng/mL. Median duration of everolimus treatment was 73 days (range 34-138). Compared to 10 historic controls, everolimus-treated patients had 11.8 times faster RHM size regression rate (slope -0.0285 vs. -0.0024; p < 0.001). The average time to 50% size reduction was 1.13 +/- 0.33 month (range 0.66-1.4 months) with everolimus versus 72.9 +/- 53.03 months in controls (p = 0.026). Following treatment with everolimus, one case was operated for congenital heart disease, without requirement of RHM resection, two others had the massive left ventricle RHM shrink to non-consequential size. The latter had a disappearance of RHM, but everolimus therapy was maintained to prevent the regrowth of a significant cerebral tumor. Everolimus is efficacious for size reduction of RHM during the neonatal period. With limited safety data, this approach should be used with caution in selective cases.