Sustained inhibition of complement C1s with sutimlimab over 2 years in patients with cold agglutinin disease.

Autor: Röth A; Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Barcellini W; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., D'Sa S; UCLH Centre for Waldenström's Macroglobulinemia and Related Conditions, University College London Hospitals NHS Foundation Trust, London, UK., Miyakawa Y; Department of Hematology, Saitama Medical University, Saitama, Japan., Broome CM; Division of Hematology, MedStar Georgetown University Hospital, Washington, DC, USA., Michel M; Henri-Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, UPEC, Créteil, France., Kuter DJ; Division of Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Jilma B; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria., Tvedt THA; Section for Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway., Weitz IC; Keck School of Medicine of USC, Los Angeles, California, USA., Yoo R; Sanofi, Cambridge, Massachusetts, USA., Jayawardene D; Sanofi, Cambridge, Massachusetts, USA., Vagge DS; IQVIA, Bangalore, India., Kralova K; Sanofi, Paris, France., Shafer F; Sanofi, Bridgewater, New Jersey, USA., Wardȩcki M; Sanofi, Warsaw, Poland., Lee M; Sanofi, Bridgewater, New Jersey, USA., Berentsen S; Department of Research and Innovation, Haugesund Hospital, Haugesund, Norway.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2023 Aug; Vol. 98 (8), pp. 1246-1253. Date of Electronic Publication: 2023 May 29.
DOI: 10.1002/ajh.26965
Abstrakt: Cold agglutinin disease (CAD) is a rare, autoimmune, classical complement pathway (CP)-mediated hemolytic anemia. Sutimlimab selectively inhibits C1s of the C1 complex, preventing CP activation while leaving the alternative and lectin pathways intact. In Part A (26 weeks) of the open-label, single-arm, Phase 3 CARDINAL study in patients with CAD and a recent history of transfusion, sutimlimab demonstrated rapid effects on hemolysis and anemia. Results of the CARDINAL study Part B (2-year extension) study, described herein, demonstrated that sutimlimab sustains improvements in hemolysis, anemia, and quality of life over a median of 144 weeks of treatment. Mean last-available on-treatment values in Part B were improved from baseline for hemoglobin (12.2 g/dL on-treatment versus 8.6 g/dL at baseline), bilirubin (16.5 μmol/L on-treatment versus 52.1 μmol/L at baseline), and FACIT-Fatigue scores (40.5 on-treatment versus 32.4 at baseline). In the 9-week follow-up period after sutimlimab cessation, CP inhibition was reversed, and hemolytic markers and fatigue scores approached pre-sutimlimab values. Overall, sutimlimab was generally well tolerated in Part B. All 22 patients experienced ≥1 treatment-emergent adverse event (TEAE); 12 (54.5%) patients experienced ≥1 serious TEAE, including seven (31.8%) with ≥1 serious infection. Three patients discontinued due to a TEAE. No patients developed systemic lupus erythematosus or meningococcal infections. After cessation of sutimlimab, most patients reported adverse events consistent with recurrence of CAD. In conclusion, the CARDINAL 2-year results provide evidence of sustained sutimlimab effects for CAD management, but that disease activity reoccurs after treatment cessation. NCT03347396. Registered November 20, 2017.
(© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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