Efficacy and Safety of Polatuzumab-Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone (Pola-R-CHP) for Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): A Real-World, Multi-Center, Retrospective Cohort Study

Introduction In the POLARIX study, Pola-R-CHP showed significant improvement in progression free survival (PFS) in previously untreated DLBCL compared to R-CHOP. Pola-R-CHP was approved for previously untreated DLBCL in China, However, there are still few reports about the efficacy and safety of Pola-R-CHP in real-world setting, leaving some questions about the optimal patient population for Pola-R-CHP. Therefore, we conducted this retrospective observational study to compare the efficacy and safety of Pola-R-CHP with R-CHOP in clinical practice. Methods The Pola-R-CHP group included previously untreated DLBCL patients who received Pola-R-CHP therapy from April 2023 to May 2024 across 5 medical centers in China. The control group included previously untreated DLBCL patients treated with R-CHOP from January 2022 to May 2024. Patients treated with Pola-R-CHP were matched by propensity scores with those treated with R-CHOP. The primary endpoint was the overall response rate (ORR) and complete response rate (CRR) at the end of treatment, and secondary endpoints were 6-month and 12-month PFS, 6-month and 12-month overall survival (OS), and severity and frequency of adverse events (AE). Results A total of 600 patients were identified, of whom 131 patients received Pola-R-CHP and 469 patients received R-CHOP. The baseline features were well balanced using a 1:2 propensity score matching method, and a total of 115 patient pairs were obtained for further survival and prognosis analysis. The ORR was 91.3% and CRR was 82.6% for patients treated with Pola-R-CHP, while 76.1% and 66.5% for patients treated with R-CHOP, respectively (P＜0.005 for both ORR and CRR comparisons). For patients treated with Pola-R-CHP, different gene mutation subgroup has different results: for double-expresser group, the CRR was 89.1% and the ORR was 93.5% ; for EZB group, the CRR was 93.3% and the ORR was 93.3%; for MCD group, the CRR was 77.3% and the ORR was 86.4%; for Non-GCB group, the CRR was 86.3% and the ORR was 94.5%；for TP53 mutation group, the CRR was 66.7% and the ORR was 85.2%. After a median follow-up of 8.53 months, the 6-month PFS was 91.3% for Pola-R-CHP and 73.4% for R-CHOP (hazard ratio (HR) = 0.305; 95% confidence interval (Cl), 0.157-0.596; P= 0.0005), the 12-month PFS was 90.1% for Pola-R-CHP and 68.1% for R-CHOP (HR= 0.297; 95% CI, 0.157-0.560; P= 0.0002). Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with Pola-R-CHP compared to R-CHOP (log-rank test, P= 0.0005 and P＜0.0001 for 6-month and 12-month PFS; P= 0.0002 and P＜0.0001 for 6-month and 12-month OS, respectively). Notably, subgroups analysis indicated that patients with age >= 60 yrs, males, Ann Arbor stage of III-IV, without B symptoms, International Prognostic Index (IPI) of 4-5, elevated β2-microglobulin levels, extranodal involvement＞2, elevated lactate dehydrogenase (LDH) levels and Ki67 expression >= 80%, had a significantly higher ORR, CRR, 6-month and 12-month PFS in the Pola-R-CHP group compared to R-CHOP group. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3 to 4 AE. The most common AE was hematological toxicity. Lymphopenia, anemia, neutropenia, and thrombocytopenia at grade 3-4 was observed in 66.41% vs 69.08%, 6.11% vs 6.18%, 7.63% vs 6.82%, and 7.63% vs 9.38% respectively in Pola-R-CHP and R-CHOP with no significant difference. In terms of non-hematologic toxicity, many cases were complicated with constipation (32.82% vs 29.42%), fatigue (22.90% vs 26.44%), ALT/AST elevation (22.14% vs 26.65%), diarrhea (19.85% vs 22.60%) and peripheral neuropathy (15.27% vs 14.29%), but only a few were grade 3-4. Prophylactic PEG-G-CSF administration was given in most of the cases. No deaths due to AE were observed. Unexpected adverse events were not observed. Conclusion In this study, patients treated with Pola-R-CHP had better treatment response, PFS, OS and controlled toxicity compared with those received R-CHOP in the real-world setting. And safety profiles were similar to POLARIX study. These findings demonstrate that Pola-R-CHP is well tolerated and the efficacy can be promising compared to R-CHOP.