Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma

Abstract

Background

Diffuse large B-cell lymphoma (DLBCL) is the most common type of Non-Hodgkin's lymphoma in the United States, with approximately 40% of first-line DLBCL chemoimmunotherapy attempts failing. The FDA approved a new type of antibody–drug conjugate (ADC), Zynlonta (loncastuximab tesirine), once called ADCT-402, on April 23, 2021, for relapsed or refractory (R/R) DLBCL. Loncastuximab tesirine comprises a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin. 

Purpose

The purpose of this article is to review the pharmacological properties of loncastuximab tesirine and evaluate its efficacy and safety in the treatment of R/R DLBCL.

Methods

In PubMed, Web of Science and CNKI, I searched for relevant literature as of November 2021 through some keywords. Obtained loncastuximab tesirine essential drug and related clinical trial information on https://www.adctherapeutics.com/ and clinicaltrials.gov.

Results

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. The results of the main non-comparative clinical trials LOTIS-1, LOTIS-2 and LOTIS-3 were encouraging. In LOTIS-1, the overall response rate (ORR) of R/R DLBCL patients treated with loncastuximab tesirine was 42.3%, and loncastuximab tesirine had excellent stability and acceptable safety profile. The recommended dosage of loncastuximab tesirine is 0.15 mg/kg every three weeks for two cycles, 0.075 mg/kg every three weeks for each subsequent cycle. The pivotal LOTIS-2 showed that loncastuximab tesirine had substantial single-agent antitumour activity in patients with R/R DLBCL: the ORR and complete response rate were 48.3% and 24.1%, respectively, and produced a durable response with acceptable safety and tolerability. The results of the LOTIS-3 phase 1 portion indicated that loncastuximab tesirine 60 µg/kg plus ibrutinib 560 mg had encouraging antitumour activity in R/R DLBCL, with an ORR of 56.7%. Haematological adverse events such as anaemia and neutropenia, non-haematological 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.

Conclusions

Loncastuximab tesirine is a CD19-targeted ADC that addresses the unmet needs of R/R DLBCL patients who have been heavily pretreated, comprising high-risk populations.