Loncastuximab in high-risk and heavily pretreated relapsed/refractory diffuse large B-cell lymphoma: a realworld analysis from 21 US centers

Abstract

Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab- teserine (Lonca) is an antibody-drug conjugate which was approved by the Food and Drug Administration for the treatment of patients with R/R DLBCL who have received at least two prior lines of therapy, based on the results of the LOTIS-2 trial. However, there are limited data regarding its efficacy in the real-world setting. This retrospective study included 21 US centers and evaluated outcomes of patients with R/R DLBCL treated with Lonca. Our analysis comprises 187 patients with notably higher-risk baseline features compared to those of the LOTIS-2 population, including a higher proportion of patients with bulky disease (17% vs. 0%), high-grade B-cell histology (22% vs. 8%), and increased number of prior lines of therapy (median 4 vs. 3). The complete response rate was 14% and overall response rate was 32%. The median event-free survival and overall survival were 2.1 and 4.6 months, respectively. Those with bulky disease and high-grade B-cell histology had significantly worse outcomes, and those with non-germinal center cell of origin and a complete response to the most recent line of therapy demonstrated superior outcomes. In summary, in this largest retrospective cohort study of Lonca in the real-world setting, the response rates, event-free survival and overall survival were lower than those reported in LOTIS-2, which is likely reflective of its use in higher risk and more heavily pre-treated patients in the real world compared to the patients enrolled on a clinical study.

Figure 1.

Forest plot for complete response and overall response by clinicopathological features at the start of treatment with loncastuximab-teserine. CR: complete response; OR: overall response; HBGL: high-grade B-cell lymphoma; GCB: germinal center B-cell; LDH: lactate dehydrogenase; CAR: chimeric antigen receptor.

Figure 2.

Outcome analysis of patients treated with loncastuximab-teserine. (A) Event-free survival for all patients. (B) Overall survival for all patients. EFS: event-free survival; OS: overall survival.

Figure 3.

Outcomes stratified by response to loncastuximab-teserine. (A) Event-free survival. The median event-free survival for patients who had a complete response, partial response, stable disease and progressive disease was not reached (NR) (9.6-NR), 6.3 (4.9-10.4), 2.8 (2.2-NR), and 0.9 (0.7-1.4) months, respectively. (B) Overall survival. The median overall survival for patients who had a complete response, partial response, stable disease and progressive disease was 12.6 (10.6-NR), 7.6 (6.2-NR), 5.3 (3.6-NR), and 2.8 (2.0-3.3) months, respectively. EFS: eventfree survival; PD: progression of disease; SD: stable disease; PR: partial response; CR: complete response; OS: overall survival.