The efficacy and safety of polatuzumab vedotin-based regimens in the treatment of diffuse large B-cell lymphoma: A retrospective real-world study

Abstract Background: Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, is characterized by high heterogeneity, strong invasiveness and poor prognosis. Although R-CHOP regimen has greatly improved the prognosis, 30–40% DLBCL patients develop relapsed/refractory disease. Polatuzumab vedotin (Pola) is an antibody-drug conjugate (ADC) targeting CD79b, a B-cell receptor component ubiquitously expressed in DLBCL. Previous clinical trials have demonstrated the superior efficacy of Pola-R-CHP regimen in DLBCL treatment. This study was conducted to further evaluate the preliminary efficacy and safety of Pola-based regimens for DLBCL patients, especially with subgroup analyses. Methods: This was a retrospective real-world study in patients with clinical and histopathological confirmed DLBCL in China. We retrospectively investigated the clinical information and treatment outcome of 109 DLBCL patients between 2023 and 2025. Adverse events (AEs) were assessed in accordance with NCI CTCAE v4.03. Results: Totally, 109 DLBCL patients receiving Pola-based regimens were enrolled in the study. The median age was 59 years (range, 17 - 80 years), with 52 males (47.7%). There were 60 cases (65.2%) with non-GCB subtypes, 73 cases (78.5%) with Ann Arbor stage III–IV, 28 patients (25.9%) with IPI score ＞3. The median treatment duration was 3.42 months (range, 1 - 10 months), and 4.55 courses (range, 1 - 11 courses). 69 patients (63.3%) underwent a full course of Pola-based regimens. Median follow-up times were 208 days (range, 26–1480 days). The toxic reactions were relatively mild, including grade 3 febrile neutropenia in 4 cases (3.7%), grade 3 neutropenia (6.4%), grade 3 thrombocytopenia (8.2%). No other grade 3-4 non-hematologic AEs were reported. In the total of 109 DLBCL patients, 101 cases had evaluable response evaluation. 41 patients (40.6%) achieved complete response (CR), and 34 patients (33.7%) achieved partial response (PR), with overall response rate (ORR) of 74.3%. Interestingly, DLBCL patients receiving Pola treatment for more than 3 months showed higher CRR (48% vs 27%) and PRR (38% vs 27%), and longer PFS (P=0.001) and OS (P=0.002), compare to these less than 3 months. Moreover, Pola treatment for more than 3 courses could improve CRR (48% vs 0%), PRR (36% vs 19%), PFS (P0.001) and OS (P0.001) in DLBCL patients. Besides, DLBCL patients underwent a full course of Pola treatment had higher CRR (49% vs 27%) and PRR (38% vs 27%), and longer PFS (P=0.002) and OS (P=0.02). These results indicated that Pola-based regimens could improve the treatment response and clinical prognosis of DLBCL patients, especially with multiple- and full- courses. To minimize the disturbance of confounding factors, 69 DLBCL patients receiving full-course Pola-based regimens were selected for further analyses. The median treatment duration was 3.62 months (range, 1 - 9 months), and 5.04 courses (range, 2 - 11 courses). 61 cases had evaluable response evaluation. 39 patients (49.2%) achieved CR, and 23 patients (37.7%) achieved PR, with overall response rate (ORR) of 86.9%. Moreover, Pola treatment for more than 3 courses showed higher CRR (52% vs 0%) and PRR (38% vs 33%). Next, we performed subgroup analyses to explore the efficacy of Pola-based regimens in different subgroups. Notably, elderly DLBCL patients (60 y) showed higher CRR (54% vs 45%) than non-elderly cases. DLBCL patients with ECOG score of 0–1 had significantly higher CRR (54% vs 27%) and PRR (40% vs 27%). Besides, the ORR was higher in Ann Arbor stage III–IV group (100% vs 80%). DLBCL patients with higher peripheral blood β-2 microglobulin (3mg/L) showed higher CRR (71% vs 45%). Furthermore, the ORR was higher in Ki6780% group (94% vs 75%). These results indicated that Pola-based regimens could achieve more clinical benefit in specific DLBCL patients, especially in elderly cases, patients with low ECOG score, advanced stage and high Ki67 expression. Conclusions: Our preliminary results suggested that Pola-based regimens may be a well-tolerated and effective regimen in DLBCL patients, which could greatly improve the treatment response in specific subgroups. These results might provide clinical medication guidance for DLBCL patients, and future studies with a large sample size and longer follow-up time are needed to validate these conclusions.