Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib
2022; Rockefeller University Press; Volume: 219; Issue: 3 Linguagem: Inglês
10.1084/jem.20212148
ISSN1540-9538
AutoresG Morin, C. Degrugillier-Chopinet, Marie Vincent, Antoine Fraissenon, H. Aubert, Célia Chapelle, Clément Hoguin, François Dubos, B. Catteau, Florence Petit, Aurélie Mezel, Olivia Domanski, Guillaume Herbreteau, Marie Alesandrini, Nathalie Boddaert, Nathalie Boutry, Christine Broissand, Tianxiang Han, Fabrice Branle, Sabine Sarnacki, Thomas Blanc, Laurent Guibaud, Guillaume Canaud,
Tópico(s)Neurofibromatosis and Schwannoma Cases
ResumoPIK3CA-related overgrowth spectrum (PROS) includes rare genetic conditions due to gain-of-function mutations in the PIK3CA gene. There is no approved medical therapy for patients with PROS, and alpelisib, an approved PIK3CA inhibitor in oncology, showed promising results in preclinical models and in patients. Here, we report for the first time the outcome of two infants with PROS having life-threatening conditions treated with alpelisib (25 mg) and monitored with pharmacokinetics. Patient 1 was an 8-mo-old girl with voluminous vascular malformation. Patient 2 was a 9-mo-old boy presenting with asymmetrical body overgrowth and right hemimegalencephaly with West syndrome. After 12 mo of follow-up, alpelisib treatment was associated with improvement in signs and symptoms, morphological lesions and vascular anomalies in the two patients. No adverse events were reported during the study. In this case series, pharmacological inhibition of PIK3CA with low-dose alpelisib was feasible and associated with clinical improvements, including a smaller size of associated complex tissue malformations and good tolerability.
Referência(s)