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

TL;DR

Narsoplimab successfully treated a severe case of TA-TMA in an adult who did not respond to eculizumab, offering hope for patients with this deadly transplant complication.

Contribution

First reported case of successful treatment of eculizumab-refractory TA-TMA using Narsoplimab in an adult.

Findings

The patient achieved complete hematological response after Narsoplimab treatment.

Narsoplimab may be effective in cases resistant to eculizumab and other therapies.

Early recognition and treatment switching improved outcomes in this case.

Abstract

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.

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