Complement is a complex innate immune system. A number of clinical disorders are linked to genetic polymorphisms and autoantibodies that cause excessive complement activation. Among these, the hematologic illness paroxysmal nocturnal hemoglobinuria (PNH) serves as a model for complement activation and inhibition.
In 2007, Eculizumab, the first-in-class complement inhibitor, was authorized for PNH. To address some unmet needs, ravulizumab, a long-acting C5 inhibitor, and pegcetacoplan, a C3 inhibitor, have both been authorized for PNH. Novel agents, such as factor B and factor D inhibitors, were investigated with encouraging results. In the era of several authorized targeted complement therapies, treatment selection must be based on a tailored strategy. Beyond PNH, complement inhibition has demonstrated effectiveness and safety in cold agglutinin illness, particularly with the C1s inhibitor of the classical complement pathway, sutimlimab, and pegcetacoplan. In addition, C5 inhibition with eculizumab and ravulizumab, as well as lectin pathway inhibition with narsoplimab, was studied in transplantation-associated thrombotic microangiopathy.
Complement inhibitors may improve other hematologic entities, such as delayed hemolytic transfusion response or immune thrombocytopenia, as a result of the next-generation complement therapy revolution. For a study, researchers sought to describe current knowledge of complement targeting in hematologic diseases, with a focus on complement biology for clinicians, complement activation, and therapeutic inhibition in prototypic complement-mediated hematologic diseases, hematologic entities under investigation for complement inhibition, and other complement-related disorders of potential interest to hematologists.
