Efficacy of BV-R2 therapy in relapsed/refractory DLBCL: A single centre preliminary retrospective analysis

Abstract Background: Patients with transplant-ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma (TIE R/R DLBCL) face poor outcomes and limited survival. The phase 3 ECHELON-3 study demonstrated significant overall survival (OS) and progression-free survival (PFS) benefits with brentuximab vedotin plus lenalidomide and rituximab (BV-R2) compared to lenalidomide-rituximab (R2) in TIE R/R DLBCL. However, the real-world applicability of these findings remains to be further explored. This retrospective study aims to evaluate the efficacy and safety of the BV-R2 regimen in a real-world setting. Methods: Eligible patients had biopsy-confirmed R/R DLBCL after ≥1 prior systemic therapy, were transplant-ineligible, and had no central nervous system involvement. The BV-R2 regimen consisted of 6 induction cycles (brentuximab vedotin 1.8 mg/kg IV day 1; lenalidomide 20 mg PO days 1-21; rituximab 375 mg/m² IV day 1; q28d). Patients achieving partial response (PR) or complete response (CR) received maintenance therapy with brentuximab vedotin (1.8 mg/kg or 50mg IV) and lenalidomide (10 mg PO days 1-21) q28d until progression or unacceptable toxicity. Bridging to CAR-T therapy was permitted. Endpoints included OS, PFS, tumor response and safety. Results: By June 2025, 12 R/R DLBCL patients from Guangdong Provincial People's Hospital in China were enrolled. The median age was 68.5 years (range, 52-88). Key characteristics: Ann Arbor stage III/IV (66.7%), non-GCB subtype (41.7%), IPI ≥3 (58.3%), and extranodal involvement (83.3%). Median prior lines of therapy was 2 (range, 1-4); 66.7% were primary refractory, and 58.3% refractory to last line. The median on-treatment cycles was 2 (range, 1-10). Of 11 efficacy-evaluable patients, the best response showed an ORR of 63.3% (CR: 27.3% 3/11, PR: 36.4% 4/11), stable disease (SD) in 18.2% (2/11; both bridged to CAR-T after cycles 1-2), and progressive disease (PD) in 18.2% (2/11). At data cutoff, 4 patients experienced PD and 1 died. Median PFS was 3.63 months (95% CI: 3.14-4.12); median OS was not reached. Treatment-related adverse events (AEs) occurred in 5 (41.7%) patients with hematologic toxicity (1 with G4 neutropenia, 2 with G4 febrile neutropenia) and 1 (8.3%) with G3 interstitial pneumonia. Toxicities were manageable, with no new safety signals identified. Conclusion: The BV-R2 regimen demonstrates encouraging efficacy and a tolerable safety profile in this initial real-world cohort of patients with TIE R/R DLBCL. Longer follow-up and a larger patient cohort are needed to validate these preliminary findings.