Sutimlimab in Cold Agglutinin Disease

Röth, Alexander; Barcellini, Wilma; D’Sa, Shirley; Miyakawa, Yoshitaka; Broome, Catherine; Michel, Marc; Kuter, David J.; Jilma, Bernd; Tvedt, Tor Henrik Anderson; Fruebis, Joachim; Jiang, Xiaoyu; Lin, Stella; Reuter, Caroline; Morales-Arias, Jaime; Hobbs, William E.; Berentsen, Sigbjørn

doi:10.1056/nejmoa2027760

Cited by 137 publications

(214 citation statements)

References 40 publications

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“…6 In CAD, where complement inhibitors are in clinical trials, a true BTH has not been defined yet, although hemolytic flares have been described under treatment. 7 Gerber et al 5 (N = 1), the second (N = 2), or after both doses (N = 2) of vaccine.…”

Section: Sars-cov-2 Vaccination Induces Breakthrough Hemolysis In Paroxysmal Nocturnal Hemoglobinuria On Complement Inhibitormentioning

confidence: 99%

SARS‐CoV‐2 vaccination induces breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria on complement inhibitor

et al. 2021

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Section: Sars-cov-2 Vaccination Induces Breakthrough Hemolysis In Paroxysmal Nocturnal Hemoglobinuria On Complement Inhibitormentioning

confidence: 99%

SARS‐CoV‐2 vaccination induces breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria on complement inhibitor

et al. 2021

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“…This may result in both IVH and EVH due to either terminal activation of complement and membrane attack complex (MAC) formation, or C3b deposition on erythrocytes and reticulo-endothelial phagocytosis. CAD is mainly treated with immunosuppressants (steroids and the anti-CD20 monoclonal antibody rituximab) and complement inhibitors are in clinical trials with promising results ( 6 ). Complement activation may be observed even in warm type AIHA (wAIHA), particularly in case of high levels of IgG anti-erythrocyte autoantibodies, resulting in DAT positivity for IgG+C.…”

Section: Introductionmentioning

confidence: 99%

Complement Mediated Hemolytic Anemias in the COVID-19 Era: Case Series and Review of the Literature

et al. 2021

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The complex pathophysiologic interplay between SARS-CoV-2 infection and complement activation is the subject of active investigation. It is clinically mirrored by the occurrence of exacerbations of complement mediated diseases during COVID-19 infection. These include complement-mediated hemolytic anemias such as paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA), particularly cold agglutinin disease (CAD), and hemolytic uremic syndrome (HUS). All these conditions may benefit from complement inhibitors that are also under study for COVID-19 disease. Hemolytic exacerbations in these conditions may occur upon several triggers including infections and vaccines and may require transfusions, treatment with complement inhibitors and/or immunosuppressors (i.e., steroids and rituximab for AIHA), and result in thrombotic complications. In this manuscript we describe four patients (2 with PNH and 2 with CAD) who experienced hemolytic flares after either COVID-19 infection or SARS-Cov2 vaccine and provide a review of the most recent literature. We report that most episodes occurred within the first 10 days after COVID-19 infection/vaccination and suggest laboratory monitoring (Hb and LDH levels) in that period. Moreover, in our experience and in the literature, hemolytic exacerbations occurring during COVID-19 infection were more severe, required greater therapeutic intervention, and carried more complications including fatalities, as compared to those developing after SARS-CoV-2 vaccine, suggesting the importance of vaccinating this patient population. Patient education remains pivotal to promptly recognize signs/symptoms of hemolytic flares and to refer to medical attention. Treatment choice should be based on the severity of the hemolytic exacerbation as well as of that of COVID-19 infection. Therapies include transfusions, complement inhibitor initiation/additional dose in the case of PNH, steroids/rituximab in patients with CAD and warm type AIHA, plasma exchange, hemodialysis and complement inhibitor in the case of atypical HUS. Finally, anti-thrombotic prophylaxis should be always considered in these settings, provided safe platelet counts.

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“…In post-HCT AIHA, eculizumab was effective in one of the three cases reported in literature [73]. Several other complement inhibitors, such as pegcetacoplan and sutimlimab, are actively being investigated in complement-mediated hemolytic anemia [116,117]. These agents may be viable options for refractory hemolytic anemia post-HCT.…”

Section: Treatmentmentioning

confidence: 99%

Post–hematopoietic stem cell transplantation immune-mediated anemia: a literature review and novel therapeutics

et al. 2022

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Anemia following allogeneic hematopoietic stem cell transplantation (HCT) can be immune- or non-immune mediated. Auto- or alloimmunity due to blood groups incompatibility remain an important cause if post-HCT immune-mediated anemia. ABO incompatibility is commonly encountered in HCT and may lead to serious clinical complications including acute hemolysis, pure red cell aplasia, and passenger lymphocyte syndrome. It remains controversial whether ABO incompatibility may affect HCT outcomes, such as relapse, non-relapse mortality, graft-versus-host disease and survival. Non-ABO incompatibility is less frequently encounterd but can have similar complications to ABO incompatibility, causing adverse clinical outcomes. It is crucial to identify the driving etiology of post-HCT anemia in order to prevent and treat this condition. This requires a comprehensive understanding of the mechanism of anemia in blood group incompatible HCT, and the temporal association between HCT and anemia. In this review, we summarized the literature on post-HCT immune-mediated anemia with a focus on ABO and non-ABO blood group incompatibility, described the underlying mechanism of anemia, and outlined preventive and treatment approaches.

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Sutimlimab in Cold Agglutinin Disease

Cited by 137 publications

References 40 publications

SARS‐CoV‐2 vaccination induces breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria on complement inhibitor

SARS‐CoV‐2 vaccination induces breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria on complement inhibitor

Complement Mediated Hemolytic Anemias in the COVID-19 Era: Case Series and Review of the Literature

Post–hematopoietic stem cell transplantation immune-mediated anemia: a literature review and novel therapeutics

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