Abstract
Introduction: The landmark POLARIX study showed that Pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen was superior to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) in previously untreated diffuse large B-cell lymphoma (DLBCL) with IPI 2-5. Notably, this study explicitly excluded patients with an IPI score of 0-1, confining the standard treatment for this subgroup to the R-CHOP regimen. However, there remains a significant unmet clinical need within this population, necessitating the exploration of novel therapeutic strategies to improve outcomes. This is attributable to the marked heterogeneity of such patients, who may present with other poor prognostic factors including bulky disease, double-expressor lymphoma (DEL), and TP53 gene mutations, coupled with their accounting for approximately 30% of the total first-line treatment population. Therefore, we conducted a nationwide multicenter real-world retrospective study in China to evaluate the Pola-R-CHP regimen in previously untreated DLBCL patients with IPI 0-1.
Methods: All patients who received at least one cycle of Pola-R-CHP as first-line therapy from 17 centers in China were screened. Those who had an IPI score of 0-1 were enrolled in this retrospective study. A whole-body 18F-FDG PET/CT scan or contrast-enhanced CT scan was performed for efficacy evaluation after 3 or 4 cycles (interim) and 6 cycles (end of treatment, EOT) of Pola-R-CHP. Treatment response was evaluated by 2014 Lugano response criteria, and adverse events (AEs) were graded according to NCI-CTCAE 5.0. The primary endpoint was the complete response (CR) rate at EOT, and secondary endpoints included overall response rate (ORR) at interim and EOT, safety, progression-free survival (PFS), and overall survival (OS).
Results: From May 2023 to August 2025, a total of 118 consecutive patients were enrolled in this study, with a median age of 53.5 years old (range: 17-87). Of these, 53 (44.9%) patients were female. Additionally, 72 (61.1%) patients had an IPI score of 1, 20 (16.9%) patients were Ann Arbor stage Ⅲ to Ⅳ, 13 (11.0%) patients were with B symptoms, 61 (51.6%) patients were of the non-GCB subtype, 11 (15.2%) patients had bulky diseases, 74 (62.6%) patients had at least one extra-nodal site, 29 (24.5%) patients had DEL, 11 (9.3%) patients had double/triple hit lymphoma (DHL or THL), and 30 (25.4%) patients showed high P53 expression. At the cut-off date July 15, 2025, the median cycle of Pola-R-CHP regimen was 6 (range: 1-8). Sixty-nine (58.3%) patients received at least 6 cycles of Pola-R-CHP. The CR rate at EOT, primary endpoint of this study, was 93.8%. The ORR at interim and EOT was 98.8% and 100%, respectively. Subgroup analyses revealed that similar response rates were observed both at the interim and EOT across various subgroups, including elderly (age over 60 years old), non-GCB, extra-nodal, DEL, DHL or THL, high P53 expression subgroups. The CR rate at EOT in patients with high P53 expression tended to be lower than overall population (84.6% vs 93.8%). The most common AEs of all grades were anemia (89.0%), leukocytopenia (61.5%) and neutropenia (51.6%), among which the most common grade 3-4 AE was neutropenia (27.5%). With a median follow-up of 7.1 months (95% Confidence Interval: 5.7-8.9), altogether 2 patients progressed due to central nervous system involvement at 7.5 and 5.7 months, respectively.
Conclusions: This investigation represents the first multicenter study addressing real-world outcomes of IPI 0-1 DLBCL patients treated with first-line Pola-R-CHP. Our results suggested that Pola-R-CHP showed excellent effectiveness and manageable toxicities for this specific population, even among those with adverse risk factors.
