P1079 - Everolimus: A novel chemotherapeutic approach for cardiac rhabdomyomas

Introduction: Cardiac rhabdomyomas are the most common neonatal intracardiac tumor. Most spontaneously regress and surgical resection is reserved for tumors causing arrythmias or significant obstruction. The use of the chemotherapeutic agent, Everolimus, for treatment of cardiac rhabdomyomas is rare, with limited representation in the literature. We present the case of a neonate with a large obstructive cardiac rhabdomyoma showing significant reduction with Everolimus treatment.

Case Description: A term infant male was born by uncomplicated vaginal delivery to a 33-year-old gravida 5 para 4 mother. Delivery was unremarkable with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively; and the infant was clinically well-appearing. Critical congenital heart disease screening after 24 hours of life revealed pre- and post- ductal oxygen saturations of 80%. The patient was started on a prostaglandin E1 (PGE1) infusion and an echocardiogram revealed multiple intracardiac tumors with the largest obstructing the right ventricular outflow tract. The patient was intubated and transferred to a level IV NICU.

Upon transfer, a subsequent echocardiogram revealed a large 23mm x 13mm tumor on the pulmonary valve, obstructing the right ventricular outflow tract. Based on tumor number and appearance, the patient was empirically diagnosed with cardiac rhabdomyomas. A trial of Everolimus was initiated on day of life (DOL) 5. Serial echocardiograms showed gradual reduction in tumor size. The patient was extubated and weaned to room air in the first week of life. PGE1 was discontinued on DOL#21, and the patient successfully maintained normal oxygen saturations following duct closure. The patient showed no significant medication side effects. A tuberous sclerosis panel was sent and was positive for the TSC2 mutation, confirming the diagnosis of tuberous sclerosis.

Discussion: Cardiac rhabdomyomas account for a large majority of all pediatric primary cardiac tumors and can be diagnosed empirically when multiple intracardiac tumors are observed in a neonate. The majority of cardiac rhabdomyomas are associated with tuberous sclerosis complex. Most cardiac rhabdomyomas spontaneously regress so conservative management is preferred. Surgical intervention has historically been the only therapeutic alternative for hemodynamically significant tumors. Use of the mTOR inhibitor, Everolimus, represents a novel approach for reducing the tumor burden of cardiac rhabdomyomas. There have been 15 published case reports and one, five patient, prospective study involving the use of Everolimus for cardiac rhabdomyomas with treatment duration for symptomatic lesions ranging from 2 months to 10 months.

Conclusion: Everolimus is an emerging therapeutic option for infants with hemodynamically significant cardiac rhabdomyomas that do not require immediate surgical management. This case represents an obstructive cardiac rhabdomyoma managed successfully with Everolimus, showcasing the most rapid regression reported in literature to date.