In-human clinical experience with direct stick embolization of low-flow vascular malformations using a mammalian target of rapamycin inhibitor

Background: Although direct stick embolization (DSE) of low-flow vascular malformations (LFVMs) with off-label embolotherapeutic compounds is the current mainstay of therapy, systemic oral mammalian target of rapamycin (mTOR) inhibition has evolved into an important adjunctive therapy that is associated with frequent blood draws, systemic toxicity, and rebound signs and symptoms upon cessation. We herein report our experience with in-human DSE of LFVMs with an mTOR inhibitor for direct, intralesional targeting of the culprit mutated pathway without repeated systemic exposure.

Methods: Since 2020, 33 procedures involving DSE were performed in 25 patients with LFVMs using a patented formulation and technique involving the intravenously compatible mTOR inhibitor Yale-OCR7737, used as a liquid compound in a collagen matrix emulsion for added viscosity and intralesional residence. Data were maintained prospectively and reviewed retrospectively for technical success (successful catheterization of the lesion and intralesional delivery of compound), clinical success (improvement in signs/symptoms with radiologically documented reduction in flow and/or volume of treated lesion), complications, side effects, and reinterventions.

Results: From 2020 to 2023, 33 procedures involving DSE were performed using Yale-OCR7737 in 25 patients (10 men [40%]; 15 women [60%]; mean age, 28 years [range, 1-70 years]) with LFMVs involving the head/neck (48%) and limbs (40%); 88% were nonsyndromic and 12% had Klippel-Trenaunay syndrome; 68% exhibited venous malformations, and 32% had lymphatic malformations. Technical and clinical success rates were 100%. Mean DSE sessions per patient was 1.4 (range, 1-5). Localized intravascular coagulopathy was present after 16 DSE procedures (49%); D-dimer improved after DSE in 7 cases. No perioperative or delayed complications occurred. Side effects were seven cases (21%) of self-limited, transient, oral aphthous ulcers.

Conclusions: Our findings suggest that DSE of LFVMs with mTOR inhibitors (Yale-OCR7737) may be safe and effective. This may represent the new embolotherapeutic frontier in the endovascular treatment of LFMVs.