Efficacy and prognosis of pola-R-CHP in CD5-positive DLBCL: Rapid response, long-term survival benefits, and early therapeutic optimization

Abstract Background and Aim: CD5-positive diffuse large B-cell lymphoma (DLBCL) represents an aggressive subtype with particularly poor clinical outcomes. Following China's approval of Pola-R-CHP (polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisone) for first-line DLBCL treatment in April 2023, this multicenter retrospective study aimed to evaluate its efficacy as initial therapy for CD5-positive DLBCL. Methods: We conducted a retrospective study involving treatment-naïve CD5-positive DLBCL patients who received Pola-R-CHP as first-line therapy between April 2023 and November 2024 at six institutions. Polatuzumab vedotin was administered 1.8 mg/KG, rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2 or epirubicin 70 mg/m2, all intravenously on Day 1. Prednisone was given 100 mg orally once daily from Day 1 to Day 5. Treatment response was evaluated through PET/CT scans after 3 cycles (interim assessment) and 6 cycles of R-chemo plus 2 cycles of R (end-of-treatment assessment). Results: In the analysis of 32 treatment-naïve CD5-positive DLBCL patients, the median age was 63.5 years (interquartile range: 52–69.8), with an equal distribution of 50% females and 50% males. Twenty-five percent of patients presented with Ann Arbor stage III disease, while 53.1% had stage IV disease. The majority (59.4%) exhibited an International Prognostic Index (IPI) score of 3 or higher, and 62.5% had two or more extranodal involvements, predominantly affecting the spleen. Tumor burden indicators, such as elevated lactic dehydrogenase and β2-microglobulin levels, were present in 71.9% and 53.1% of patients, respectively. Additionally, 75% of patients were classified as non-germinal center B-cell subtype according to the Hans algorithm, and 31.3% were diagnosed with double-expressor lymphoma. All patients underwent a minimum of three treatment cycles and received interim PET/CT evaluations. Following a median follow-up period of 17.9 months, the overall response rate (ORR) and complete response rate (CRR) after three cycles were 100% (32/32) and 75% (24 /32), respectively. By the end of treatment, the ORR and CRR were 92.6% (28/30) and 76.7% (23/30), respectively. Of the eight patients who achieved partial remission (PR) after 3 cycles, one attained complete remission (CR) by cycle 6, five maintained PR, one experienced disease progression, and one remained under treatment without completing 6 cycles. Notably, two of the eight patients succumbed to fatal disease progression despite salvage therapy with CAR-T cells and CD20×CD3 bispecific antibodies. Among the 25 patients who achieved CR after 3 cycles, 23 maintained remission at the final PET/CT assessment, while two relapsed from CR by end-of-treatment evaluation, and one remains under ongoing treatment. In the cohort, 10 out of 32 patients (31.3%) experienced Grade 3 and 4 adverse events (AEs), with neutropenia being the predominant issue. Additional reported side effects comprised peripheral neuropathy and thrombocytopenia. Conclusions: CD5-positive DLBCL patients demonstrated rapid responses to Pola-R-CHP, with the regimen exhibiting a favorable safety profile. Patients failing to achieve CR at interim evaluation are unlikely to attain CR by treatment completion, suggesting a potential need for earlier therapeutic modification.