CD5 positivity and aberrant P53 expression predict primary refractoriness to first-line pola-R-CHP in patients with diffuse large B-cell lymphoma

Abstract Background: The Pola-R-CHP regimen has emerged as an effective initial treatment for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Nevertheless, a subset of patients demonstrates suboptimal responses. Identifying risk factors for primary refractoriness to Pola-R-CHP is essential for risk stratification and therapeutic decision-making. Aims: This study aimed to investigate clinical and biological predictors of poor response to Pola-R-CHP in a real-world cohort. Methods: We conducted a retrospective analysis of 78 patients with newly diagnosed DLBCL, who underwent up to six cycles of Pola-R-CHP as their initial treatment between May 2023 and March 2025. The patients were divided into two groups based on their treatment response: primary refractory group was characterized by the inability to achieve a partial response after 3 cycles or a complete response after 6 cycles, or by disease progression during treatment. Baseline clinical and laboratory variables were compared between these groups. To identify potential risk factors for poor response, we employed univariate Cox regression and multivariate binary logistic regression analyses. Results: Among the 78 patients, 19 (24.4%) were classified as the primary refractory group, while 59 were categorized as the treatment-effective group. Compared to those in the treatment-effective group, patients in the primary refractory group exhibited higher frequencies of advanced-stage disease (100% vs. 76.3%, P=0.045), CD5 positivity (31.6% vs. 6.8%, P=0.016), and aberrant P53 protein expression (≤1% or ≥80%) (63.2% vs. 33.9%, P=0.024). However, there were no statistically significant differences between the two groups in terms of gender (male) (42.1% vs. 59.3%, P=0.189), age (65.8±10.8 vs. 64.2±11.5 years, P=0.597), IPI score ≥2 (89.5% vs. 74.6%, P=0.294), presence of B symptoms (57.9% vs. 45.8%, P=0.357), number of extranodal sites ≥3 (47.4% vs. 25.4%, P=0.071), white blood cell count, hemoglobin level (5.8±2.1 vs. 6.3±1.9 ×106/L, P=0.324), platelet count (247.4±92.7 vs. 239.4±85.1 ×106/L, P=0.728), lactate dehydrogenase level (536.3±281.9 vs. 404.5±346.7 U/L, P=0.146), β2-microglobulin level (3.6±1.6 vs. 2.9±1.4 mg/L, P=0.076), or the proportion of double-expressor DLBCL (47.4% vs. 25.4%, P=0.238). In multivariate logistic regression, both CD5 positivity (P=0.016) and aberrant P53 expression (P=0.013) emerged as independent predictors of primary refractoriness. Conclusion: In patients with newly diagnosed DLBCL treated with frontline Pola-R-CHP, CD5 positivity and aberrant P53 protein expression are significant independent risk factors for primary refractory disease. These biomarkers may aid in early risk stratification and support consideration of alternative or intensified therapeutic strategies for the high-risk populations.