Efficacy and safety of loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a systematic review and meta-analysis.

Abstract

Background: Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) remains a therapeutic challenge, particularly for patients ineligible for stem-cell transplantation or CAR T-cell therapy. Loncastuximab tesirine, a CD19-directed antibody-drug conjugate, has demonstrated promising single-agent activity in recent studies and is approved in this setting. In this meta-analysis, we aim to assess the efficacy and safety of loncastuximab tesirine monotherapy in patients with R/R DLBCL.

Methods: A systematic review was conducted per PRISMA 2020 guidelines, searching PubMed, Embase, and Cochrane CENTRAL from inception until March 2025. Studies reporting clinical outcomes of loncastuximab tesirine monotherapy with defined efficacy and safety endpoints were included. Seven studies met the inclusion criteria, including three clinical trials and four observational cohort studies. Two reviewers independently extracted data. Pooled analyses were conducted in R (version 4.5.1) using absolute risk and random-effects modeling. Heterogeneity was assessed using the I² statistic; publication bias was evaluated via Egger's test and funnel plots.

Results: The pooled overall response rate (ORR) was 47.3% (95% CI 33.5-61.3%), and the complete response (CR) rate was 22.0% (95% CI 16.7-27.7%). One-year overall survival (OS) and progression-free survival (PFS) were 48.2% (95% CI 17.8-79.3%) and 31.2% (95% CI 9.2-58.9%), respectively, with substantial heterogeneity across studies. In the clinical trial subgroup, ORR and CR were 47.3% (95% CI 33.3-61.5%) and 23.9% (95% CI 21.9-26.1%), while 1-year OS and PFS were 43.8% (95% CI 25.2-63.3%) and 28.0% (95% CI 14.6-43.8%), respectively. No publication bias was detected. Treatment-emergent adverse events (AEs) occurred in 98.7% of patients, with grade ≥ 3 events in 82.6%. Common hematologic AEs included anemia (47.7%; grade ≥ 3: 13.6%), leukopenia (16%, grade ≥ 3: 9.7%), neutropenia (32.9%; grade ≥ 3: 22.4%), and thrombocytopenia (24.3%; grade ≥ 3: 16.1%). Frequent non-hematologic AEs included fatigue (20%), fever (15.6%), vomiting (12.4%), and abdominal pain (11.4%). Other reported events included hypokalemia (25.5%), rash (20%), and peripheral edema (23.7%).

Conclusion: This meta-analysis supports the efficacy of loncastuximab tesirine monotherapy in heavily pretreated R/R DLBCL, with an ORR of ~ 47% and manageable toxicity. These findings reinforce its role as a valuable treatment option in patients with limited alternatives and highlight the need for randomized studies to optimize patient selection and sequencing strategies.