Long-term effects of sirolimus treatment for slow-flow vascular malformations: Real-world evidence from the French observational multicentre SIROLO study

Cécilia Maillet; Olivia Boccara; Stéphanie Mallet; Didier Bessis; Christine Labrèze; Sorilla Mary-Prey; Laurent Guibaud; Annouk Bisdorff; Anne Dompmartin; Juliette Mazereeuw-Hautier; Christine Chiaverini; Thomas Hubiche; Bertille Bonniaud; Caroline Degrugillier-Chopinet; Anne-Claire Bursztejn; Hélène Aubert; Maella Severino; Sophie Leducq; Mathilde Tardieu; Aline Joly; Grégoire Boulouis; Anne Le Touze; Arnaud Paré; Elsa Tavernier; Annabel Maruani

doi:10.1111/jdv.20385

Long-term effects of sirolimus treatment for slow-flow vascular malformations: Real-world evidence from the French observational multicentre SIROLO study

J Eur Acad Dermatol Venereol. 2024 Nov 25. doi: 10.1111/jdv.20385. Online ahead of print.

Authors

Cécilia Maillet^{1

2}, Olivia Boccara³, Stéphanie Mallet⁴, Didier Bessis⁵, Christine Labrèze^{6

7}, Sorilla Mary-Prey^{6

7}, Laurent Guibaud⁸, Annouk Bisdorff⁹, Anne Dompmartin¹⁰, Juliette Mazereeuw-Hautier¹¹, Christine Chiaverini¹², Thomas Hubiche¹², Bertille Bonniaud¹³, Caroline Degrugillier-Chopinet¹⁴, Anne-Claire Bursztejn¹⁵, Hélène Aubert¹⁶, Maella Severino¹¹, Sophie Leducq^{1

2

17}, Mathilde Tardieu¹⁸, Aline Joly^{1

19}, Grégoire Boulouis^{1

20}, Anne Le Touze^{1

21}, Arnaud Paré^{1

19}, Elsa Tavernier^{17

22}, Annabel Maruani^{1

2

17}

Affiliations

¹ Unit of Pediatric Dermatology, Department of Dermatology, University Hospital Center (CHRU) of Tours, Tours, France.
² Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Tours), Tours, France.
³ Department of Dermatology and Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), AP-HP, Paris University, Necker-Enfants Malades Hospital, Paris Centre University, Imagine Institute, Paris, France.
⁴ Department of Dermatology, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France.
⁵ Department of Dermatology, University Hospital Center (CHU) of Montpellier, Montpellier, France.
⁶ Department of Dermatology, University Hospital Center (CHU) of Bordeaux, Bordeaux, France.
⁷ BRIC (BoRdeaux Institute of onCology), UMR1312, INSERM, University of Bordeaux, Bordeaux, France.
⁸ University Hospital Center (CHU) Lyon, Mère-Enfant Hospital, Reference Center for Superficial Vascular Anomalies, Lyon Bron, France.
⁹ Department of Neuroradiology/Vascular Anomalies Clinic, AP-HP, Lariboisière Hospital, Paris, France.
¹⁰ Department of Dermatology, University Hospital Center (CHU) of Caen, University Caen-Normandie, Caen, France.
¹¹ Department of Dermatology, University Hospital Center (CHU) of Toulouse, Reference Center for Rare Skin Diseases, Paul Sabatier University, Toulouse, France.
¹² Department of Dermatology, Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC-Sud), University Hospital Center (CHU) of Nice, Nice, France.
¹³ Department of Dermatology, University Hospital Center (CHU) of Dijon, Dijon, France.
¹⁴ Department of Cardiovascular Functional Explorations and Pediatric Cardiology, Coeur-Poumons Institute, University Hospital Center (CHRU) of Lille, Lille, France.
¹⁵ Department of Dermatology and Allergology, University Hospital Center (CHU) of Nancy, Brabois Hospital, Nancy, France.
¹⁶ Department of Dermatology, University Hospital Center (CHU) of Nantes, Nantes, France.
¹⁷ INSERM 1246-SPHERE, University of Tours & University of Nantes, Tours, France.
¹⁸ Department of Dermatology, University Hospital Center (CHU) of Grenoble-Alpes, Couple Enfant Hospital, Grenoble, France.
¹⁹ Department of Maxillofacial Surgery, University Hospital Center (CHRU) of Tours, Tours, France.
²⁰ Department of Interventional Neuroradiology, University Hospital Center (CHRU) of Tours, Tours, France.
²¹ Department of Pediatric Surgery, University Hospital Center (CHRU) of Tours, Clocheville Hospital, Tours, France.
²² Clinical Investigation Center (CIC) INSERM 1415, University Hospital Center (CHRU) of Tours, Tours, France.

PMID: 39584318
DOI: 10.1111/jdv.20385

Abstract

Rationale: Sirolimus is a treatment for slow-flow vascular malformations (SFVMs). However, the long-term management remains challenging.

Objectives: The SIROLO study assessed the long-term effects and real-life management of oral sirolimus for SFVMs by investigating data from 15 French tertiary centres for vascular anomalies.

Methods: Participants were retrospectively included if they had a SFVM that was being/had been treated with sirolimus for at least 3 years in total. Data were collected on treatment goals when initiating sirolimus, investigator-reported efficacy, safety, dosages and treatment withdrawal.

Results: The cohort involved 67 patients with various SFVM entities (mean [±SD] age 19.6 ± 12.5 years, 35 children, 52.2%). We found a heterogeneity of predefined treatment goals, the most frequent being cessation of pain. The investigators considered that sirolimus had persistent efficacy for bleeding, ulceration and pain but only slight efficacy for reducing volume. It was reported to be well-tolerated, although serious adverse events (mainly infections and also two ovarian cysts) were reported in 6 patients (9.0%) and required definitive sirolimus discontinuation for one. Overall, 11 patients (16.4%) had at least one temporary withdrawal period, leading to symptom recurrence and sirolimus resumption at a mean of 6.4 ± 9.6 months. The mean sirolimus concentration was 6.4 ± 3.7 ng/mL during the first 6 months and decreased over time (mean concentration during the last 6 months: 4.2 ± 3.2 ng/mL), probably to target the minimal efficient dosage. Eight patients (11.9%) switched to alpelisib because of insufficient efficacy of sirolimus.

Conclusion: This real-life study gives answers to frequent questions patients and parents ask before sirolimus initiation for SFVMs, such as persistence of efficacy over time, long-term side effects and time to recurrence in case of withdrawal.