On April 23, 2021, the FDA approved loncastuximab tesirine-lpyl (Zynlonta; ADC Therapeutics), a CD19-directed antibody–drug conjugate, for the treatment of adults with relapsed or refractory large B-cell lymphoma after ≥2 lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. The FDA granted loncastuximab tesirine priority review and an orphan drug designation for this indication.
The FDA approval of loncastuximab tesirine was based on results from the multicenter, open-label, single-arm, phase 2 LOTIS-2 clinical trial of 145 patients with relapsed or refractory DLBCL who had received ≥2 lines of systemic therapy. Patients received intravenous loncastuximab tesirine 0.15 mg/kg every 3 weeks for 2 cycles, followed by 0.075 mg/kg every 3 weeks for subsequent cycles, until progressive disease or unacceptable toxicity.
The overall response rate (ORR) was 48.3% (95% confidence interval [CI], 39.9-56.7) with a complete response rate of 24.1% (95% CI, 17.4-31.9). After a median follow-up of 7.3 months, median response duration was 10.3 months (95% CI, 6.9-not evaluable).
“Single-agent Zynlonta demonstrated clinically important outcomes in the pivotal LOTIS-2 study across several disease subtypes. Notably, this included transplant-eligible and ineligible patients and patients who previously received stem cell transplant or CAR-T cell therapy,” said Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University.
The most common (≥20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.