Antibody-Drug Conjugate Addresses Unmet Need in R/R DLBCL

Loncastuximab tesirine is an effective therapy that addresses the unmet needs of patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), according to a review in the European Journal of Clinical Pharmacology.

Approved by the US Food and Drug Administration in April 2021 for adults with R/R DLBCL, loncastuximab tesirine (Zynlonta) is a monoclonal antibody conjugate medication.

“Once it binds with cells expressing CD19, loncastuximab tesirine is internalized by the cell and then releases SG3199, which irreversibly binds to the DNA, thereby disrupting the basic DNA metabolism process and ultimately leading to cell death,” wrote author Bo Xu, of the University of South China College of Pharmacy.

In addition to explaining the pharmacological properties of loncastuximab tesirine, the review looked at its efficacy and safety in the treatment of patients with R/R DLBCL in 3 noncomparative clinical trials: LOTIS-1, LOTIS-2, and LOTIS-3.

Results were encouraging, according to the review. LOTIS-1 showed an 42.3% overall response rate among patients with R/R DLBCL treated with the medication, which had an acceptable safety profile and excellent stability. LOTIS-2 reported substantial single-agent antitumor activity in the patient population, with a 48.3% overall response rate and a 24.1% complete response rate. Safety and tolerability were acceptable, and response was durable.

Phase 1 of LOTIS 3 identified encouraging antitumor activity in R/R DLBCL and a 56.7% overall response rate.

“Hematological adverse events such as anemia and neutropenia, nonhematological events such as fatigue and nausea, and biochemical events such as γ-glutamyl transferase increase, and blood alkaline phosphatase increases were common after administration of loncastuximab tesirine,” the author reported.

Reference:
Xu B. Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. Eur J Clin Pharmacol. Published online ahead of print January 21, 2022. doi:10.1007/s00228-021-03253-3