Loncastuximab tesirine 10mg powder for solution for infusion vials

INTRODUCTION: Despite recent approvals of new treatments, relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains challenging to treat, with limited durable responses and a high proportion of patients relapsing after two or more lines of therapy. Loncastuximab tesirine (Lonca) is a highly potent CD19-targeted antibody drug conjugate with convenient dosing for patients with third-line R/R DLBCL. METHODS: In the absence of head-to-head trials, unanchored matching-adjusted indirect comparisons (MAICs) were conducted to compare the relative efficacy and safety of Lonca with polatuzumab vedotin + bendamustine and rituximab (Pola + BR). RESULTS: Four studies included in the MAICs were identified via systematic review and hand-searching. Lonca (LOTIS-2) was compared with three comparator studies for Pola + BR (GO29365 extension study, COTA database, Dal et al. 2023). Overall, there was no evidence of a difference in overall response and complete response (CR) rates. Despite Pola + BR demonstrating a higher CR rate in the GO29365 extension study, this did not translate into significant improvements in progression-free or overall survival. Survival analyses indicated similar efficacy between treatments across studies, with most comparisons/meta-analyses showing no statistically significant differences. Lonca had significantly lower odds of Grade 3-4 infections, any serious adverse event (SAE), and specific SAEs including febrile neutropenia, pneumonia and pyrexia. Of the safety endpoints analyzed, none indicated significant differences in favor of Pola + BR. CONCLUSION: These results suggest no evidence of a difference in efficacy between the two treatments and potentially more favorable safety profile for Lonca compared with Pola + BR in patients with R/R DLBCL after two or more lines of treatment.

Abstract licence: CC BY-NC 4.0

BackgroundRelapsed/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.MethodsA 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.ResultsThe 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%).ConclusionThis 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.

Abstract licence: CC BY-NC-ND 4.0