ICML 2025 | What do the initial results from the LOTIS-7 trial suggest for loncastuximab tesirine plus glofitamab in R/R DLBCL?

During the 18th International Conference on Malignant Lymphoma (ICML), Jun 17–21, 2025, Lugano, CH, the Lymphoma Hub was pleased to speak with Juan Pablo Alderuccio, University of Miami, Florida, US. We asked, What do the initial results from the LOTIS-7 (NCT04970901) trial suggest for loncastuximab tesirine plus glofitamab in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL)?

In this interview, Alderuccio discussed preliminary data presented at the 18th ICML Congress 2025 from the LOTIS-7 clinical trial, a multicenter study exploring novel combination therapies in relapsed or refractory B-cell lymphomas. The discussion focused on the combination of loncastuximab tesirine plus glofitamab, highlighting initial findings on safety, efficacy, and potential implications for patients with DLBCL.

Key learnings¹

• The LOTIS-7 trial is a multicenter study evaluating the combination of loncastuximab tesirine with other agents, including glofitamab, in R/R DLBCL.

• In the dose-escalation phase, patients received glofitamab at 90, 120, and 150 µg/kg, as well as the standard dose of loncastuximab.

• The overall response rate across all dose levels was 93.3%, with a complete response (CR) rate of 86.7%.

• The time to first complete response was 42 days at the 150 µg/kg dose level, compared with 80 days at the 120 µg/kg level.

• The median duration of response had not yet been reached at the time of the preliminary analysis.

• Among the patients who received at least one dose, the most common adverse event was neutropenia, observed in 24.4%. Other AEs of interest included anemia, elevated liver enzymes, and thrombocytopenia, though these were reported infrequently.

• Neutropenia was the most common cause of dose delays; however, only one patient required a dose reduction of loncastuximab.

• The incidence of cytokine release syndrome (CRS) was low, with the majority being Grade 1.

• Based on efficacy and CRS data, the dose expansion part of the trial will proceed with the 150 µg/kg dose.

• Estimated enrollment for the dose-expansion cohort is 100 patients.

• This combination offers an off-the-shelf alternative for patients ineligible for or unable to access chimeric antigen receptor (CAR) T-cell therapy.

• To better assess the depth and durability of response, additional follow up is necessary, including circulating tumor DNA analysis.