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. 2024 Aug;59(8):1161-1168.
doi: 10.1038/s41409-024-02305-3. Epub 2024 May 21.

Safety and efficacy of narsoplimab in pediatric and adult patients with transplant-associated thrombotic microangiopathy: a real-world experience

Marta Castelli  1 , Maria Caterina Micò  2 , Anna Grassi  2 , Alessandra Algarotti  2 , Federico Lussana  1   2 , Maria Chiara Finazzi  2 , Benedetta Rambaldi  2 , Chiara Pavoni  2 , Giuliana Rizzuto  2 , Paola Tebaldi  3 , Francesca Vendemini  4 , Marta Verna  4 , Sonia Bonanomi  4 , Andrea Biondi  4   5 , Adriana Balduzzi  4   5 , Alessandro Rambaldi  6   7 , Giacomo Gotti  4
Affiliations

Safety and efficacy of narsoplimab in pediatric and adult patients with transplant-associated thrombotic microangiopathy: a real-world experience

Marta Castelli et al. Bone Marrow Transplant. 2024 Aug.

Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication following hematopoietic stem cell transplantation (HSCT). No approved treatments are currently available. This study presents real-world data obtained with narsoplimab, a human immunoglobulin G4 monoclonal antibody that inhibits MASP-2, the effector enzyme of the lectin pathway of the complement system. Between January 2018 and August 2023, 20 (13 adult and 7 pediatric) patients diagnosed with TA-TMA received narsoplimab under an ongoing compassionate use program. The diagnosis was based on internationally defined criteria for pediatric and adult patients. Fifteen patients fulfilled the criteria recently established by an international consensus on TA-TMA. Nineteen patients exhibited high-risk characteristics. Thirteen patients (65%) responded to narsoplimab, achieving transfusion independence and significant clinical improvement. The one-hundred-day Overall Survival (OS) post-TA-TMA diagnosis was 70%, and 100% for responders. Narsoplimab proved to be effective and safe in the treatment of high-risk TA-TMA, with no increased infectious complications or other safety signals of concern across all age groups. The high response rates and the encouraging survival outcomes underscore the potential of narsoplimab as a valuable therapeutic option, particularly for high-risk cases.

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Conflict of interest statement

MCM: Novartis: Honoraria. AB: Neovii: Speakers Bureau; Medac: Speakers Bureau; Agmen: Speakers Bureau; Novartis: Speakers Bureau. AB: Colmmune: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Agmen: Speakers Bureau; BMS: Membership on an entity’s Board of Directors or advisory committees; Novartis: Speakers Bureau; Galapagos: Membership on an entity’s Board of Directors or advisory committees. FL: Amgen: Speakers Bureau; Pfizer: Membership on an entity’s Board of Directors or advisory committees and Speakers Bureau; Incyte: Speakers Bureau; Bristol Myers Squibb: Membership on an entity’s Board of Directors or advisory committees and Speakers Bureau; AbbVie: Membership on an entity’s Board of Directors or advisory committees; Clinigen Membership on an entity’s Board of Directors or advisory committees. AR: Astellas: Honoraria; Pfizer: Honoraria; Agmen: Honoraria; Omeros: Honoraria; Novartis: Honoraria; Kite-Gilead: Honoraria; Jazz: Honoraria; Celgene-BMS: Honoraria; Janssen: Honoraria; Roche: Honoraria; Incyte: Honoraria; ABBVIE: Honoraria. GG: Omeros: Congress Support.

Figures

Fig. 1
Fig. 1. Histological confirmation of TA-TMA on intestinal (sigmoid A/B) and gastric (C/D) biopsy in two adult patients.
a Loss of glands in the colon mucosa, characterized by the disappearance and atrophy of glands. Mucosal denudation, involving the loss of surface epithelium, often replaced by a single layer of regenerative enterocytes. b Widespread sloughing of epithelial cells and perivascular hemorrhages in the mucosa, indicated by the extravasation of red blood cells (RBC) from capillaries in the lamina propria. c Necrosis of the gastric mucosa and extensive ulceration. d Endothelial cell swelling, characterized by the enlargement of endothelial cells in the capillaries of the lamina propria. Sparse fungal elements in the vast necrotic area. Diffuse perivascular mucosal hemorrhage.
Fig. 2
Fig. 2. Overall survival of the cohort of pediatric and adult patients treated with narsoplimab.
Overall Survival from TA-TMA diagnosis (a) and from transplant date (b).
See this image and copyright information in PMC

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