The Anti-CD19 Antibody–Drug Conjugate Loncastuximab Tesirine

Abstract

The therapiesbispecificB-cell surface targetingantibodyantigen CD19constructs haveCD19 shownandwaschimericidentified efficacyantigen inseveral the treatmentreceptordecadesT ofcells.ago B-cellasLoncastuximab malignancies,a valuable targettesirine includingforisimmunotherapy.an Fc-engineeredanti-CD19 antibody–drugSeveral monoclonalantibody-based antibodies,conjugate that delivers a pyrrolobenzodiazepine dimer payload. Preclinical studies demonstrated that loncastuximab tesirine has activity against B-cell lymphoma in vitro and in vivo. The initial phase I trial of loncastuximab tesirine in relapsed/refractory (r/r) B-cell lymphomas included 183 patients, and although there were no dose-limiting toxicities, loncastuximab tesirine presented a specific pattern of adverse events, including oedema and effusions (31.7%), elevation in gamma-glutamyl transferase without transaminase elevation (31.1%) and rash (24.6%). In a phase II trial conducted in r/r diffuse large B-cell lymphoma (n=145), loncastuximab tesirine resulted in an overall response rate of 48.3% (24.1% complete response) and median duration of response of 13.4 months. Outcomes were comparable among different disease risk groups, including elderly patients, and those with transformed indolent lymphoma and double-hit lymphoma. Given its single-agent activity and safety profile, loncastuximab tesirine is a valuable therapeutic alternative against B-cell malignancies. Multiple ongoing trials are investigating its role in combination regimens and other indications. This article reviews the development of loncastuximab tesirine and summarizes the results from published and ongoing trials.