A Multi-Targeted Strategy for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: Real-World Outcomes of the ViPOR...

Background/Objectives: Relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs) remain a major therapeutic challenge, particularly in patients with aggressive subtypes and limited treatment options after multiple lines of therapy. The ViPOR regimen, a multi-targeted combination of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide, has demonstrated promising activity in early-phase studies; however, real-world data are limited. Methods: We conducted a retrospective, two-center study including patients with R/R B-NHL treated with the ViPOR regimen between January 2024 and April 2026. Clinical characteristics, treatment responses, survival outcomes, and safety data were analyzed. Results: A total of 14 patients were included, with a median age of 45 years and a median of 3.5 prior lines of therapy. Most patients had advanced-stage disease (71% stage IV), and 36% had primary refractory disease. The interim overall response rate (ORR) was 62%, including 31% complete response (CR) and 31% partial response. At the end of treatment, the ORR was 54%, with a CR rate of 54%. Radiotherapy was incorporated in selected patients with residual disease and contributed to response deepening. Six patients (43%) were successfully bridged to allogeneic stem cell transplantation, all in CR. Responses were notably more favorable in the activated B-cell (ABC) subtype compared to the germinal center subtype. The most common adverse events were neutropenia (57%) and diarrhea (36%), and the regimen demonstrated a manageable safety profile. During follow-up, 57% of patients remained alive. Conclusions: The ViPOR regimen demonstrated promising efficacy and acceptable safety in heavily pretreated R/R B-NHL, particularly in the ABC subtype. Its ability to induce deep responses and enable bridging to allogeneic stem cell transplantation highlights its potential role in real-world clinical practice. Larger prospective studies are warranted to confirm these findings.