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Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial
Sutimlimab, a first-in-class humanized immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits the classical complement pathway at C1s, rapidly halted hemolysis in the single-arm CARDINAL study in recently transfused patients with cold agglutinin disease (CAD). CADENZA was a 26-week r...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437710/ https://www.ncbi.nlm.nih.gov/pubmed/35687757 http://dx.doi.org/10.1182/blood.2021014955 |
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author | Röth, Alexander Berentsen, Sigbjørn Barcellini, Wilma D’Sa, Shirley Jilma, Bernd Michel, Marc Weitz, Ilene C. Yamaguchi, Masaki Nishimura, Jun-ichi Vos, Josephine M. I. Storek, Michael Wong, Nancy Patel, Parija Jiang, Xiaoyu Vagge, Deepthi S. Wardęcki, Marek Shafer, Frank Lee, Michelle Broome, Catherine M. |
author_facet | Röth, Alexander Berentsen, Sigbjørn Barcellini, Wilma D’Sa, Shirley Jilma, Bernd Michel, Marc Weitz, Ilene C. Yamaguchi, Masaki Nishimura, Jun-ichi Vos, Josephine M. I. Storek, Michael Wong, Nancy Patel, Parija Jiang, Xiaoyu Vagge, Deepthi S. Wardęcki, Marek Shafer, Frank Lee, Michelle Broome, Catherine M. |
author_sort | Röth, Alexander |
collection | PubMed |
description | Sutimlimab, a first-in-class humanized immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits the classical complement pathway at C1s, rapidly halted hemolysis in the single-arm CARDINAL study in recently transfused patients with cold agglutinin disease (CAD). CADENZA was a 26-week randomized, placebo-controlled phase 3 study to assess safety and efficacy of sutimlimab in patients with CAD without recent (within 6 months prior to enrollment) transfusion history. Forty-two patients with screening hemoglobin ≤10 g/dL, elevated bilirubin, and ≥1 CAD symptom received sutimlimab (n = 22) or placebo (n = 20) on days 0 and 7 and then biweekly. Composite primary endpoint criteria (hemoglobin increase ≥1.5 g/dL at treatment assessment timepoint [mean of weeks 23, 25, 26], avoidance of transfusion, and study-prohibited CAD therapy [weeks 5-26]) were met by 16 patients (73%) on sutimlimab, and 3 patients (15%) on placebo (odds ratio, 15.9 [95% confidence interval, 2.9, 88.0; P < .001]). Sutimlimab, but not placebo, significantly increased mean hemoglobin and FACIT-Fatigue scores at treatment assessment timepoint. Sutimlimab normalized mean bilirubin by week 1. Improvements correlated with near-complete inhibition of the classical complement pathway (2.3% mean activity at week 1) and C4 normalization. Twenty-one (96%) sutimlimab patients and 20 (100%) placebo patients experienced ≥1 treatment-emergent adverse event. Headache, hypertension, rhinitis, Raynaud phenomenon, and acrocyanosis were more frequent with sutimlimab vs placebo, with a difference of ≥3 patients between groups. Three sutimlimab patients discontinued owing to adverse events; no placebo patients discontinued. These data demonstrate that sutimlimab has potential to be an important advancement in the treatment of CAD. This trial was registered at www.clinicaltrials.gov as #NCT03347422. |
format | Online Article Text |
id | pubmed-9437710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-94377102022-11-16 Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial Röth, Alexander Berentsen, Sigbjørn Barcellini, Wilma D’Sa, Shirley Jilma, Bernd Michel, Marc Weitz, Ilene C. Yamaguchi, Masaki Nishimura, Jun-ichi Vos, Josephine M. I. Storek, Michael Wong, Nancy Patel, Parija Jiang, Xiaoyu Vagge, Deepthi S. Wardęcki, Marek Shafer, Frank Lee, Michelle Broome, Catherine M. Blood Clinical Trials and Observations Sutimlimab, a first-in-class humanized immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits the classical complement pathway at C1s, rapidly halted hemolysis in the single-arm CARDINAL study in recently transfused patients with cold agglutinin disease (CAD). CADENZA was a 26-week randomized, placebo-controlled phase 3 study to assess safety and efficacy of sutimlimab in patients with CAD without recent (within 6 months prior to enrollment) transfusion history. Forty-two patients with screening hemoglobin ≤10 g/dL, elevated bilirubin, and ≥1 CAD symptom received sutimlimab (n = 22) or placebo (n = 20) on days 0 and 7 and then biweekly. Composite primary endpoint criteria (hemoglobin increase ≥1.5 g/dL at treatment assessment timepoint [mean of weeks 23, 25, 26], avoidance of transfusion, and study-prohibited CAD therapy [weeks 5-26]) were met by 16 patients (73%) on sutimlimab, and 3 patients (15%) on placebo (odds ratio, 15.9 [95% confidence interval, 2.9, 88.0; P < .001]). Sutimlimab, but not placebo, significantly increased mean hemoglobin and FACIT-Fatigue scores at treatment assessment timepoint. Sutimlimab normalized mean bilirubin by week 1. Improvements correlated with near-complete inhibition of the classical complement pathway (2.3% mean activity at week 1) and C4 normalization. Twenty-one (96%) sutimlimab patients and 20 (100%) placebo patients experienced ≥1 treatment-emergent adverse event. Headache, hypertension, rhinitis, Raynaud phenomenon, and acrocyanosis were more frequent with sutimlimab vs placebo, with a difference of ≥3 patients between groups. Three sutimlimab patients discontinued owing to adverse events; no placebo patients discontinued. These data demonstrate that sutimlimab has potential to be an important advancement in the treatment of CAD. This trial was registered at www.clinicaltrials.gov as #NCT03347422. American Society of Hematology 2022-09-01 /pmc/articles/PMC9437710/ /pubmed/35687757 http://dx.doi.org/10.1182/blood.2021014955 Text en © 2022 by The American Society of Hematology. https://creativecommons.org/licenses/by-nc-nd/4.0/Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
spellingShingle | Clinical Trials and Observations Röth, Alexander Berentsen, Sigbjørn Barcellini, Wilma D’Sa, Shirley Jilma, Bernd Michel, Marc Weitz, Ilene C. Yamaguchi, Masaki Nishimura, Jun-ichi Vos, Josephine M. I. Storek, Michael Wong, Nancy Patel, Parija Jiang, Xiaoyu Vagge, Deepthi S. Wardęcki, Marek Shafer, Frank Lee, Michelle Broome, Catherine M. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial |
title | Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial |
title_full | Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial |
title_fullStr | Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial |
title_full_unstemmed | Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial |
title_short | Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial |
title_sort | sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 cadenza trial |
topic | Clinical Trials and Observations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437710/ https://www.ncbi.nlm.nih.gov/pubmed/35687757 http://dx.doi.org/10.1182/blood.2021014955 |
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