P1-238 - Clinical efficacy of mTOR inhibitor for Kaposiform hemangioendotheliomas with Kasabach-Merritt phenomenon

Abstract

Kasabach-Merritt phenomenon (KMP) is a life-threatening, consumptive coagulopathy associated with underlying kaposiform hemangioendothelioma (KHE) in infancy. The mortality rate from hemorrhagic complications of KMP can be as high as 30% and patients often require multidrug or multimodal regimens. The mammalian target of rapamycin (mTOR) activates protein synthesis, resulting in numerous cellular processes including cell proliferation and increased angiogenesis, thus playing a key role in the pathogenesis of various vascular anomalies. The purpose of this study is to evaluate the safety and efficacy of mTOR inhibitors (sirolimus and everolimus) in the treatment of patients with KHE with KMP. Informed consent was obtained and approved by our ethical committee. This study analyzed combined data from a systematic retrospective review of medical records of patients treated with sirolimus and everolimus between 2014 and 2017. Sirolimus was given at 0.01mg/day daily orally and subsequently adjusted to achieve serum levels between 5 and 15 ng/ml. Disease improvement was determined by radiologic imaging (volumetric MRI) and clinical status assessments (severity score). Side effects were noted according to CTCAE v4. 3 patients (4, 5, 6 months of age) had KHE with KMP and reached 6 months follow-up. All patient's showed improvement of thrombocytopenia and coagulopathy within 7 days. All patients platelet count returned to normal and coagulopathy resolved. All their tumor showed partial response of radiological response, however no patients had complete resolution of radiologic disease. Most common side effects were mucositis and reversible hypertriglyceridemia. mTOR inhibitors, sirolimus and everolimus may suppress tumor cell growth and modulate coagulopathies. Prospective studies are needed to define the best systemic therapies for KHE with KMP and the optimal duration of treatment.