| Abstract: |
<p>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.</p> |
