Loncastuximab Tesirine Versus Polatuzumab Vedotin Plus Bendamustine and Rituximab in Relapsed/Refractory DLBCL After ≥ 2 Lines of Therapy: Matching-Adjusted Indirect Comparison.

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.