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3543 Clinical Safety and Efficacy of Narsoplimab in Pediatric and Adult Patients with Transplant-Associated Thrombotic Microangiopathy: A Real-World Experience

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, Therapies, Adverse Events, Monoclonal Antibody Therapy
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Marta Castelli1*, Maria Caterina Mico'2*, Anna Grassi3*, Alessandra Algarotti2*, Maria Chiara Finazzi2*, Benedetta Rambaldi, PhD2*, Cristian Meli2*, Giuliana Rizzuto2*, Chiara Pavoni2*, Francesca Vendemini4*, Marta Verna4*, Sonia Bonanomi4*, Adriana Balduzzi5, Andrea Biondi, MD6, Alessandro Rambaldi2 and Giacomo Gotti, MD4*

1Department of Oncology and Hematology, University of Milan and Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
2Department of Oncology-Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
3Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
4Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
5School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
6School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy


Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication occurring after hematopoietic stem cell transplantation (HSCT), often resulting in high morbidity and mortality. There are currently no approved treatments for TA-TMA, but complement inhibition is increasingly recognized as an active treatment option in this setting. Narsoplimab (OMS721) is a fully human IgG4 antibody that binds MASP-2, the effector enzyme of the lectin pathway of the complement system. A recent pivotal trial demonstrated the safety and efficacy of narsoplimab in patients with TA-TMA. We report the results of a real-world experience with narsoplimab in a series of pediatric and adult patients with TA-TMA.

Material and methods

The diagnosis of TA-TMA was based on the following criteria (Schoettler ML, et al. Transplant Cell Ther. 2023 Mar;29(3):151-163): anemia (failure to achieve transfusion independence, hemoglobin decline by ≥1 g/dL or new-onset transfusion dependence); thrombocytopenia (failure to achieve platelet engraftment, transfusion dependence, or ≥50% reduction in baseline platelet count after full platelet engraftment); elevated lactate dehydrogenase (LDH); decreased serum haptoglobin; schistocytes in the peripheral blood smear; hypertension; and proteinuria (≥1 mg/mg random urine protein-to-creatinine ratio [rUPCR]). A positive direct Coombs test was an exclusion criterion. Narsoplimab was administered intravenously at the dose of 4 mg/kg (max 370 mg) twice weekly for at least eight doses. Response criteria were defined by improvement in both laboratory TMA markers and any clinical benefit (Khaled SK, et al. J Clin Oncol. 2022 Aug;1;40(22):2447-2457).


Fifteen patients with a median age of 61 years (range, 6 - 71), 11 adults and 4 pediatrics, were treated under a compassionate use program, after ethical committee approval, between January 2018 and April 2023. All patients had previously undergone allogeneic HSCT (Table 1). All patients presented at least 4 of the 6 criteria for TA-TMA diagnosis. Fourteen patients (93%) were defined as high-risk TA-TMA for the presence of the following criteria: LDH > 2 times the ULN, rUPCR ≥ 1 mg/mg, multiorgan dysfunction, concurrent acute GvHD ≥ grade 2, or infection.

Time from transplant to TA-TMA was 161 days (range, 30 - 452). Before TA-TMA, all patients had acute GvHD with a median of 116 days (range, 21 - 405) after transplant. Severe infection had been documented in 10 patients (67%) after transplant. CMV reactivation and BK virus hemorrhagic cystitis occurred in 5 and 4 patients, respectively. Twelve patients (80%) were on calcineurin inhibitors at TA-TMA onset. Fourteen patients (93%) were transfusion dependent at baseline. Patients received a median of 11 (range, 8-34) doses of narsoplimab. All infusions were well-tolerated, and no narsoplimab-related adverse events were reported.

Eleven patients responded to treatment (73%), based on the achievement of transfusion independence (10 patients) as well as on clinical and laboratory improvement, which occurred in all responders. Before and after narsoplimab, the median hemoglobin values were 9,1 g/dL (range, 7,7 - 12,3) and 10,35 g/dL (range, 9,2 - 12,4); the median platelet count was 25.000/mmc (range, 10.000 - 62.000) and 76.000/mmc (range 32.000 - 367.000); the median LDH values were 497 U/L (range 271 - 1201) and 224 U/L (range 184 - 393), respectively. The median time to response was 50 days (range, 9 - 105). One-hundred-day survival was 80% in the study population and 100% for responders (Figure 1). After treatment completion, TA-TMA never reoccurred. Three of the four patients who failed to respond, eventually died with laboratory and clinical evidence of persisting TA-TMA.


In this study of high-risk TA-TMA patients, the inhibition of the lectin pathway of complement activation with narsoplimab was shown to be not only an effective but also a remarkably safe treatment option with no evidence of an increased risk of infectious complications in both children and adults.

Disclosures: Mico': Novartis: Honoraria. Balduzzi: Neovii: Speakers Bureau; Medac: Speakers Bureau; Agmen: Speakers Bureau; Novartis: Speakers Bureau. Biondi: 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. Rambaldi: 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.

*signifies non-member of ASH