Abstract
Loncastuximab tesirine-lpyl (ADC Therapeutics) is an anti-CD19 antibody-drug conjugate which consists of anti-CD19 antibody and cytotoxic alkylating agent, SG3199. Data from preclinical in vitro and animal studies demonstrated its selectivity and efficacy. The phase I LOTIS-1 study for relapsed, refractory B-cell non-Hodgkin lymphoma (NHL) demonstrated efficacy and a tolerable safety profile, with major adverse effects being neutropenia, thrombocytopenia, elevated liver enzymes, and fluid accumulation. Based on pharmacokinetics analysis in this study, a dose of 150 μg/kg every 3 weeks for cycles 1 and 2 followed by 75 μg/kg every 3 weeks until disease progression or intolerability was chosen for the phase II LOTIS-2 study. This study recruited relapsed, refractory diffuse large B-cell lymphoma and confirmed similar safety profile. Overall response rate was 48.6% (24.1% complete response), and overall survival was 9.9 months. Due to its safety and efficacy reported in the above trials, loncastuximab tesirine was recently approved by the US Food and Drug Administration for the treatment of relapsed, refractory diffuse large B-cell lymphoma. Several clinical trials are ongoing to assess its safety and efficacy in NHL in various clinical settings.