FDA approval of CD19-targeted ADC, loncastuximab tesirine-Ipyl, for patients with R/R large B-cell lymphoma

On April 23, 2021, it was announced that the U.S. Food and Drug Administration (FDA) approved the use of loncastuximab tesirine-lpyl, an antibody–drug conjugate (ADC), for the treatment of adult patients with relapsed and refractory (R/R) large B-cell lymphoma who have had ≥2 lines of therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high grade B-cell lymphoma.¹ This approval was based on the results of the phase II LOTIS-2 trial (NCT03589469), previously reported on the Lymphoma Hub.

Loncastuximab tesirine-Ipyl is a CD19-targeted antibody and alkylating agent conjugate designed to target and kill CD19-expressing malignant B cells. LOTIS-2 is a single-arm, multicenter trial in 145 adult patients with R/R diffuse large B-cell lymphoma (DLBCL) who received ≥2 prior lines of systemic therapy. Treatment with loncastuximab tesirine-Ipyl resulted in an overall response rate of 48.3% and a complete response rate of 24.1%. The median duration of response was 10.3 months. The most common Grade ≥3 treatment-emergent adverse events (in ≥10% of patients) included neutropenia (26.2%), thrombocytopenia (17.9%), increased gamma-glutamyltransferase (17.2%), and anemia (10.3%).

This approval is the first for an CD19-targeted ADC as single-agent therapy for R/R DLBCL.¹

On May 5, 2021, loncastuximab tesirine-lpyl was added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for the treatment of B-cell lymphomas. As a result, the agent now represents a category 2A treatment option for patients with DLBCL who have relapsed following ≥2 lines of systemic therapy.²