Michele Cavo, MD, PhD, Bologna University School of Medicine, Bologna, Italy, discusses a number of post hoc subgroup analyses in the Phase II HORIZON trial (NCT02963493) of melphalan flufenamide (meflufen) plus dexamethasone in relapsed/refractory (R/R) multiple myeloma. Melflufen is an aminopeptidase-targeted peptide-drug conjugate that releases alkylating agents into tumor cells. In the overall study population, the combination therapy showed significant efficacy and manageable tolerability, despite being a difficult to treat cohort with high rates of triple-class-refractoriness. A subgroup analysis of patients with high-risk cytogenetics found that melflufen plus dexamethasone was efficacious in this population, and has a safety profile consistent to that of the overall population. Additionally, in an analysis of patients with prior alkylator therapy exposure, melflufen showed beneficial activity, demonstrating that its mechanism of action is distinct to that of other alkylators. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.