Use of narsoplimab for eculizumab-refractory adult transplant-associated thrombotic microangiopathy (TA-TMA)

Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication associated with hematopoietic stem cell transplant (HSCT). Endothelial dysfunction and complement activation cause consumptive thrombocytopenia with intravascular hemolysis, resulting in end-organ damage, especially to the kidneys and lungs. There are no U.S. Food and Drug Administration (FDA)-approved agents for TA-TMA, although Eculizumab is the most commonly used agent to treat TA-TMA. Patients who do not respond to Eculizumab have a dismal prognosis, with reported mortality up to 80%. Narsoplimab, a mannan-binding lectin-associated serine protease-2 (MASP-2) inhibitor, has been shown to treat TA-TMA by inhibiting the lectin pathway of the complement cascade. We report the first adult case with successful management of eculizumab-refractory TA-TMA with Narsoplimab. Our patient received a matched unrelated donor (bone marrow) allogenic HSCT and subsequently developed multi-organ damage. He was refractory to numerous treatments, including eculizumab, steroids, rituximab, and plasma exchange. After developing diffuse Alveolar hemorrphage and renal failure, he was initiated on Narsoplimab and later achieved a complete hematological response and became transfusion independent. This case highlights the importance of early recognition of TA-TMA and the need to switch therapy to other complement inhibitors if resistance to Eculizumab is noted.