INTRODUCTION: Felzartamab is a novel, fully human CD38 monoclonal antibody, currently in development for the treatment of antibody-mediated rejection (AMR) following kidney transplantation. AREAS COVERED: This review focuses on current phase II trials of felzartamab in AMR and other immune-mediated kidney diseases. Specifically, it discusses the drug's mechanism of action, current phase of clinical development, potential future applications and regulatory status. EXPERT OPINION: CD38 is an activation marker expressed on the surface of plasma cells and immune cells, including natural killer cells (NK cells) cells. In a recent phase II randomized, placebo-controlled clinical trial, felzartamab demonstrated an acceptable safety and side-effect profile in patients with AMR after kidney transplantation. Efficacy outcomes suggested potential therapeutic benefits, including significant reductions in morphologic and molecular AMR activity. Given the mixed results of previous clinical trials for AMR treatments, the novel approach of targeting both antibody-secreting plasma cells and innate effector cells such as CD38