Therapy Produces Durable Responses in Patients With R/R DLBCL

Nearly half of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in a Phase 2 trial had complete or partial response to loncastuximab tesirine, according to a study published online ahead of print in The Lancet Oncology. 

“Patients with R/R DLBCL who do not respond to or who have progressive disease after salvage therapies have a poor prognosis,” researchers wrote in the study background. “Loncastuximab tesirine is a CD19-directed antibody-drug conjugate with encouraging phase 1 single-agent antitumor activity and acceptable safety in non-Hodgkin lymphoma.” 

The open-label, single-arm phase 2 trial included 145 patients with R/R DLBCL from 28 hospitals in the United States, United Kingdom, Italy, and Switzerland. The study included patients at high risk of a poor prognosis, such as double-hit, triple-hit, transformed, or primary refractory DLBCL.

For up to 1 year, participants received intravenous loncastuximab tesirine on the first day of each 21-day cycle, at 150 μg/kg for two cycles and at 75 μg/kg afterward. 

The overall response rate to loncastuximab tesirine was 48.3%, the study found, with 35 patients achieving complete response and another 35 patients showing partial response. 

The most common grade 3 or higher treatment-emergent adverse events were neutropenia, which affected 26% of patients, thrombocytopenia, which affected 18%, and increased gamma-glutamyltransferase, which occurred in 17%.  

In all, 39% of participants experienced serious adverse events. Although eight patients had treatment-emergent adverse events with a fatal outcome, none were considered related to loncastuximab tesirine, according to the study. 

“Loncastuximab tesirine has substantial single-agent antitumor activity and produces durable responses with an acceptable safety profile,” researchers concluded, “potentially offering a new therapeutic option for heavily pretreated patients with R/R DLBCL.”

Reference:
Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial [published online ahead of print, 2021 May 11]. Lancet Oncol. 2021;S1470-2045(21)00139-X. doi:10.1016/S1470-2045(21)00139-X