Current State of Drug Therapies for Antibody-mediated Rejection After Heart Transplantation

Antibody-mediated rejection (AMR) continues to be a significant and challenging complication after alternative surgical methods, contributing significantly to morbidity and mortality. Despite its clear clinical impact, there is no consensus on optimal treatment strategies due to a paucity of prospective clinical trials and the immunologic nuances of this rejection phenotype. Therapeutic plasma exchange and intravenous immunoglobulin remain the cornerstones of most AMR protocols. However, there is growing evidence supporting the use of additional therapies that target more specific antibody mechanisms. Anti-CD20 antibodies, proteasome inhibitors, anti-CD38 antibodies, interleukin-6 receptor antagonists, and complement inhibitors have been used to reverse AMR and mitigate its deleterious consequences. However, these medications come with their own nuances and considerations for use. Therefore, the purpose of this review was to provide practical "how-to" information on the use of these agents, including prescribing, dosing strategies, monitoring approaches, and duration of treatment. In addition, a key focus was placed on adverse effects profiles associated with AMR treatment with these novel agents through monitoring and risk mitigation approaches to ensure patient safety. In this way, our review aims to serve as a comprehensive and practical guide for clinicians, synthesizing existing data on both standard and emerging AMR therapies to improve patient outcomes after heart transplantation.