Orphanet journal of rare diseases · 2025
Personalized sirolimus regimen for vascular malformations: a retrospective analysis of VASE cohort.
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Seront Emmanuel, Van Damme An, Coulie Julien, Vikkula Miikka, Boon Laurence M
Аннотация
BACKGROUND: The mTOR inhibitor Sirolimus was shown to improve symptoms in patients with slow-flow vascular malformations, but long-term continuous use is limited by cumulative toxicity. A personalized approach with intermittent regimens may offer similar efficacy with fewer adverse effects (AE). This retrospective analysis evaluated the effectiveness and safety of individualized sirolimus strategies in patients who experienced symptom recurrence after completing the 2-year course in the VASE phase III trial. All patients initially resumed continuous sirolimus for 3 months, then transitioned to one personalized regimen based on their pain profiles: intermittent sirolimus 5 days-ON/2 days-OFF (Group A), hybrid intermittent plus on-demand (Group B), or fully on-demand administration triggered by pain or known stressors (Group C).
RESULTS: Thirty adults were included (Group A: n = 13; Group B: n = 6; Group C: n = 11). Across all groups, intermittent, hybrid or on-demand sirolimus maintained pain control comparable to continuous administration, significantly reducing pain intensity, crisis frequency, and crisis duration from baseline. AEs decreased from 73-85% during continuous therapy to 9-33% with intermittent/on-demand regimens, with no reported grade ≥3 event.
CONCLUSION: Personalized intermittent sirolimus regimens may effectively control symptoms and substantially reduce toxicity in patients with vascular malformations. This strategy supports individualized, long-term therapy and merits prospective validation.
TRIAL REGISTRATION: NCT02638389 and EudraCT 2015-001703-32.
RESULTS: Thirty adults were included (Group A: n = 13; Group B: n = 6; Group C: n = 11). Across all groups, intermittent, hybrid or on-demand sirolimus maintained pain control comparable to continuous administration, significantly reducing pain intensity, crisis frequency, and crisis duration from baseline. AEs decreased from 73-85% during continuous therapy to 9-33% with intermittent/on-demand regimens, with no reported grade ≥3 event.
CONCLUSION: Personalized intermittent sirolimus regimens may effectively control symptoms and substantially reduce toxicity in patients with vascular malformations. This strategy supports individualized, long-term therapy and merits prospective validation.
TRIAL REGISTRATION: NCT02638389 and EudraCT 2015-001703-32.