Simple SummaryThis paper deals with Belantamab mafodotin, a novel anti-BCMA antibody-drug conjugate licensed by regulatory agencies for the treatment of anti-CD38-refractory multiple myeloma patients. In addition to describing the mechanism of action and general information about the drug, this review mostly focuses on real-life data from American, Asian and European experiences on it. The aim of this overview is to picture an updated scenario on Belantamab mafodotin in different completed or ongoing clinical trials, studying it in different settings. Furthermore, this paper would like to provide precise data collection about the efficacy and safety of Belantamab mafodotin real-world data, showing the reproducibility of randomized clinical trial data that is also in real-life settings.AbstractDespite the recent approval of novel immunotherapies, such as immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable, and the acquisition of triple-refractoriness leads to really dismal outcomes in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody–drug conjugate, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial, and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials and also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real-life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations.