Single-Agent Loncastuximab Tesirine Shows Durable Efficacy and Safety in R/R DLBCL Treatment

In patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) loncastuximab tesirine (lonca; Zynlonta) was found to be a sustainable single agent with durable responses and an acceptable safety profile, according to results from a study published in The Lancet Oncology.¹

The LOTIS-2 (NCT03589469) study is a multicenter, open-label, single-arm phase 2 clinical trial that looked at the safety and efficacy of single agent lonca in adult patients with relapsed or refractory DLBCL who had 2 or more multi-agent treatments prior to this study. LOTIS-2 enrolled 145 patients with an ECOG performance score of 0-2 and included patients with high-risk characteristics such as, double- and triple-hit, transformed, and primary refractory DLBCL. The coprimary end points of the study were overall response and tolerability.

An analysis of the trial found an overall response rate (ORR) of 48.3% with 70 patients having a complete or partial response (95% CI, 39.9%–56.7%). Thirty-five patients had a complete response, and 35 patients had a partial response with a median duration of response at 10.3 months. A post-hoc analysis also showed that the median time to first response on lonca was 41 days. Of the patients considered high-risk enrolled on the trial patients who had disease progression after CER-T therapy had an ORR of 46.2% on lonca. Patients with double- or triple- hit DLBCL had a 33.3% ORR, while patients with transformed DLBCL had a 44.8% ORR to the CD19-directed antibody–drug conjugate.

“Patients with relapsed or refractory DLBCL who have been heavily pretreated and have difficult-to-treat disease represent an urgent area of medical need that newly approved Zynlota is now able to address,” said Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, lead author of the study in a press release. “The LOTIS-2 study established that Zynlota demonstrated substantial single-agent activity and produced durable responses with an acceptable safety profile in this patient population.”²

Patients on the trial were given 0.15 μg/kg of lonca intravenously for 2 cycles, then 0.075 μg/kg afterward on the first day of a 21 day cycle for up to 1 year, until disease relapse or progression or unacceptable toxicity.¹ Lonca was determined to have an acceptable safety profile with the most common grade 3 or higher treatment-emergent adverse event (TEAE) being 26% of patients experiencing neutropenia.

Other TEAEs included thrombocytopenia (18%) and increased gamma-glutamyltransferase (17%). Serious adverse events were found in 39% of patients while a fatal outcome occurred in 8 patients due to TEAE, however, none of the fatal outcomes were related to lonca.

Lonca was granted an accelerated approval by the FDA for patients with relapsed or refractory DLBCL who progressed after 2 or more systemic treatments as well as patients with DLBCL not specified, patients with relapsed or refractory.3 The approval was based off the LOTIS-2 study with this study bolstering the FDA’s approval.

“We are proud to have the results of our LOTIS-2 trial published in a prestigious peer-reviewed journal,” said Jay Feingold, MD, PhD, senior vice president and chief medical officer at ADC Therapeutics, the manufactures of lonca, in the release.² “On the heels of the FDA approval, this further reinforces the value of Zynlota as the first CD19-targeted ADC single-agent treatment for relapsed or refractory DLBCL and the potential for it to become the standard-of-care for third-line plus DLBCL patients in need of new treatment options.”

_References

1. _{Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. Published online May 11, 2021. doi: 10.1016/S1470-2045(21)00139-X}
2. _{ADC Therapeutics Announces Online Publication of LOTIS-2 Results in The Lancet Oncology. News release. May 12, 2021. Accessed May 17, 2021. https://bit.ly/3flNrfi}
3. _{FDA grants accelerated approval to loncastuximab tesirine-lpyl for large B-cell lymphoma. News release. April 23, 2021. Accessed May 17, 2021. https://bit.ly/2Qv2zyw}