Narsoplimab Results in Excellent Survival in Adults and Children With Hematopoietic Cell Transplant Associated Thrombotic Microangiopathy (TA‐TMA)

Inappropriate complement activation is a key driver of hematopoietic cell transplant‐associated thrombotic microangiopathy (TA‐TMA). Treatment with narsoplimab, an inhibitor of MASP‐2, the effector enzyme of the lectin pathway, resulted in a response rate of 61% in a Phase 2 clinical trial in adults with TA‐TMA. Given these promising results, a global expanded access program (EAP) was established facilitating compassionate use treatment. Herein, we report the survival of children (< 16 years old) and adults (≥ 16 years old) enrolled in the EAP from October 2017 to October 2023 (n = 136). Among children (n = 50), the majority underwent allogeneic HCT (n = 44); 37 were considered high‐risk (HR) and 30 (81.1%) had organ dysfunction at the time of TA‐TMA diagnosis. One‐year overall survival (OS) in pediatric allogeneic recipients with HR TA‐TMA who received narsoplimab as first‐line therapy (n = 12) was 75.0% and 56.2% in those who received treatment as ≥ second‐line (n = 25, 20 refractory to eculizumab). One‐year OS in the six children with a solid tumor who underwent an autologous HCT was 80%. Among the 86 adults, 84 received an allogeneic HCT, 65 had HR TA‐TMA and, among them, 57 (87.7%) had organ dysfunction at diagnosis. One‐year OS in allogeneic adults with HR TA‐TMA who received narsoplimab as first line therapy (n = 49) was 58.0%, and 40.5% in those who received narsoplimab as ≥ second line therapy (n = 16). There were no concerning safety signals. In this real‐world study enriched with patients with severe TA‐TMA, survival was excellent in children and adults, supporting the use of narsoplimab.