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Alpelisib to treat CLOVES syndrome, a member of the PIK3CA-related overgrowth syndrome spectrum
  • Gemma Garreta Fontelles,
  • Júlia Pardo Pastor,
  • Carme Grande Moreillo
Gemma Garreta Fontelles
University Hospital MutuaTerrassa
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Júlia Pardo Pastor
University Hospital MutuaTerrassa
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Carme Grande Moreillo
University Hospital MutuaTerrassa
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Abstract

CLOVES syndrome is a rare congenital overgrowth disorder caused by mutations in the phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) gene. It is part of the PIK3CA-related overgrowth syndrome (PROS) spectrum and its treatment is challenging. PROS malformations have traditionally been treated by surgery, but research into pharmacological treatments capable of blocking the PIK/AKT/mTOR pathway has increased over the past decade. Its favorable results in these settings suggest that its compassionate use in patients with PROS disorders could have clinical benefits. Another promising drug is Alpelisib, which is a selective inhibitor that competitively binds to the p110a subunit of PIK3 in the intracellular PI3K/AKT signaling pathway. A low dose of Alpelisib used on compassionate grounds was shown in an uncontrolled case series to have striking effects in a cohort of 19 PROS patients, several with life-threatening complications. Moreover, the low dose of Alpelisib provoked few side effects and did not impair linear growth of the often young patients. We present the case of a patient with CLOVES syndrome who was started on compassionate treatment with Alpelisib after surgical debulking of a cystic lymphangioma and treatment with sirolimus. This promising drug significantly reduced the size of the lymphangioma and prevented progression of the tissue overgrowth in the gluteal region. This case suggest that there may even be collateral benefits of low-dose PI3K inhibition beyond mitigating disease-specific features of PROS.

Peer review status:IN REVISION

04 Dec 2021Submitted to British Journal of Clinical Pharmacology
06 Dec 2021Assigned to Editor
06 Dec 2021Submission Checks Completed
07 Dec 2021Reviewer(s) Assigned
01 Jan 2022Review(s) Completed, Editorial Evaluation Pending
01 Jan 2022Editorial Decision: Revise Minor