Loncastuximab tesirine produced durable responses in heavily pretreated patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to data published in The Lancet Oncology.1

Loncastuximab tesirine is a CD19-directed antibody-drug conjugate that previously showed antitumor activity in a phase 1 study of patients with non-Hodgkin lymphoma.2

In the phase 2 LOTIS-2 trial (ClinicalTrials.gov Identifier: NCT03589469), researchers evaluated loncastuximab tesirine in patients with relapsed/refractory DLBCL who had previously received 2 or more multiagent systemic therapies. The study was conducted in 28 hospitals in the United States, United Kingdom, Italy, and Switzerland.

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The study enrolled 145 patients with high-risk characteristics for poor prognosis, including double-hit, triple-hit, transformed, or primary refractory DLBCL. All the participants received at least 1 dose of loncastuximab tesirine.

The overall response rate was 48.3%, with 35 patients achieving a complete response and 35 having a partial response. The median time to first response was 41.0 days.

The median duration of response was 10.3 months overall, 13.4 months for patients with a complete response, and 5.7 months for patients with a partial response.

The median progression-free survival was 4.9 months, and the median overall survival was 9.9 months.

The most common grade 3 or higher treatment-emergent adverse events (TEAEs) were neutropenia (26%), thrombocytopenia (18%), and increased gamma-glutamyl transferase (17%).

Serious TEAEs occurred in 39% of patients. Fatal TEAEs occurred in 6% of patients, but these events were considered unrelated or unlikely to be related to loncastuximab tesirine.

“The durable clinical antitumor activity of single-agent loncastuximab tesirine compared with recently approved therapies, including activity in difficult-to-treat subgroups, suggest it could change practice as a potential treatment option for patients with relapsed or refractory DLBCL who have received two or more previous systemic therapies,” the study authors wrote.

“These results are of particular importance because, to our knowledge, this trial included a broader sample of difficult-to-treat patients than did studies of other therapies approved for patients with relapsed or refractory DLBCL.”

Disclosures: This research was supported by ADC Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. 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. Lancet Oncol. 2021;22(6):790-800. doi:10.1016/S1470-2045(21)00139-X
  2. Hamadani M, Radford J, Carlo-Stella C, et al. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2021;137(19):2634-2645. https://doi.org/10.1182/blood.2020007512