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

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.

CONCLUSIONS

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.