Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data

Abstract

Loncastuximab tesirine-lpyl (ADC Therapeutics) is an anti-CD19 antibody-drug conjugate which consists of anti-CD19 antibody and cytotoxic alkylating agent, SG3199. Data from preclinical in vitro and animal studies demonstrated its selectivity and efficacy. The phase I LOTIS-1 study for relapsed, refractory B-cell non-Hodgkin lymphoma (NHL) demonstrated efficacy and a tolerable safety profile, with major adverse effects being neutropenia, thrombocytopenia, elevated liver enzymes, and fluid accumulation. Based on pharmacokinetics analysis in this study, a dose of 150 μg/kg every 3 weeks for cycles 1 and 2 followed by 75 μg/kg every 3 weeks until disease progression or intolerability was chosen for the phase II LOTIS-2 study. This study recruited relapsed, refractory diffuse large B-cell lymphoma and confirmed similar safety profile. Overall response rate was 48.6% (24.1% complete response), and overall survival was 9.9 months. Due to its safety and efficacy reported in the above trials, loncastuximab tesirine was recently approved by the US Food and Drug Administration for the treatment of relapsed, refractory diffuse large B-cell lymphoma. Several clinical trials are ongoing to assess its safety and efficacy in NHL in various clinical settings.

Revolutionizing Cancer Treatment - The Emergence and Impact of Antibody-Drug Conjugates (ADCs): A Systematic Review

“…Many patients that are r/r have poor prognoses, necessitating alternative therapies as approximately 40% of frontline treatments fail. Loncastuximab tesirine, a novel ADC comprising a humanized igG1, anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer warhead, was approved by the FDA in 2021 for r/r DLBCL after two or more systemic therapies [34]. It works by binding to CD19 on B-cells, facilitating internalization and release of the cytotoxic payload SG3199, which forms DNA crosslinks, leading to cell death.…”

Drug-Resistance Mechanism and New Targeted Drugs and Treatments of Relapse and Refractory DLBCL

“… 87 Loncastuximab tesirine is a CD19-targeted ADC and delivers cytotoxic alkylating agent, SG3199. 88 A phase II trial studied the efficacy and safety of loncastuximab tesirine in R/R DLBCL. A total of 145 patients received at least one dose of loncastuximab tesirine, with an overall response rate of 48.3%.…”

Safety of loncastuximab tesirine‐lpyl in diffuse large B‐cell lymphoma with severe hepatic dysfunction

“…4 Loncastuximab tesirine-lpyl is a novel antibody-drug conjugate consisting of an anti-CD19 antibody and an alkylating pyrrolobenzodiazepine agent, SG3199. 5,6 It received accelerated US Food and Drug Administration approval for relapsed/refractory (r/r) DLBCL on the basis of LOTIS-2. 7 In clinical practice, loncastuximab tesirine-lpyl is most commonly used for transplant-ineligible patients who do not respond to salvage therapy or have relapsed disease after autologous hematopoietic cellular therapy.…”

“…The prognosis of DLBCL remains poor, especially for patients with disease refractory to salvage therapy or those who are ineligible for adoptive cellular therapies 4 . Loncastuximab tesirine‐lpyl is a novel antibody–drug conjugate consisting of an anti‐CD19 antibody and an alkylating pyrrolobenzodiazepine agent, SG3199 5,6 . It received accelerated US Food and Drug Administration approval for relapsed/refractory (r/r) DLBCL on the basis of LOTIS‐2 7 .…”