Effectiveness and safety of polatuzumab vedotin in real-world clinical practice in Chinese patients with diffuse large B-cell lymphoma (POLAREAL): An interim analysis from a prospective, multicenter, observational registry study

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Polatuzumab vedotin (Pola) has shown significant anti-tumor activity and a manageable safety profile in DLBCL patients. Given the strict eligibility criteria in pivotal trials, real-world evidence in Chinese DLBCL patients is needed to guide clinical practice. Methods: The POLAREAL study (NCT05954910) is a prospective, observational, multicenter registry study designed to evaluate the effectiveness and safety of Pola-based regimens in Chinese patients, with a target enrollment of 1,000 patients. Eligible patients with DLBCL (aged ≥ 18 years) were enrolled and classified into three cohorts: Cohort 1-previously untreated patients classified as unfit or frail (defined as aged ≥ 80 years or < 80 years but with comorbidities and intolerance to standard dose chemotherapy); Cohort 2-previously untreated patients not meeting unfit/frail criteria; and Cohort 3-patients with relapsed/refractory disease. The primary objective was progression-free survival (PFS). Secondary objectives included best response (BCRR/BORR), overall survival (OS) and safety, etc. Results: From August 2023 to February 2025, 794 patients were enrolled and included in the full analysis set, comprising 116 patients in Cohort 1 (median age 76.1; range 44–91), 377 patients in Cohort 2 (median age 59.6; range 18–80), and 301 patients in Cohort 3 (median age 63.2; range 19–90). From cohort 1 to 3, 94.9%, 76.7% and 83.6% of patients had an IPI score of 2-5 respectively. The majority of patients (92.2%, 86.7% and 87.4% for each cohort) had the DLBCL-NOS subtype. The study also included patients typically excluded from clinical trials, such as primary mediastinal B-cell lymphoma and primary cutaneous DLBCL-leg type. The non-GCB subtypes predominated over the GCB subtype, accounted for 61.2% (Cohort 1), 54.9% (Cohort 2) and 54.8% (Cohort 3) of the patients. Double-expressor lymphoma was identified in 28.4%, 27.1% and 24.9% in each group. Additionally, transformed DLBCL-primarily arising from follicular lymphoma-was observed in 5.2%, 6.1% and 11.0% of patients across the three cohorts. In Cohort 3, 27.6% of patients had relapsed disease, while 72.4% had refractory disease. In real-world settings, the median time from the initial DLBCL diagnosis to the initiation of Pola treatment was 0.49 months (range 0-26.3) in Cohort 1 and 0.36 months (range 0-5.1) in Cohort 2, respectively. The most commonly used backbone regimens included Pola-R-mini(reduced) CHP and Pola-R in Cohort 1; Pola-R-CHP and Pola-R-DA EPCH in Cohort 2; Pola-BR, Pola-R-GemOx and Pola-R-ICE in Cohort 3. The median treatment cycles of Pola-based regimen in those patients with EOT were 6, 6 and 3 separately. The median follow-up time was 3.9 months (range 0.0-17.6), 3.2 months (range 0.0-14.7), and 2.9 months (range 0.0-11.6) across the three cohorts, respectively. As the PFS data were not mature at the time of cutoff, BORR and BCRR were reported among patients with evaluable responses including PET-CT data. In Cohort 1, the BORR was 90.7% (95% CI 81.7-96.2), and the BCRR was 62.7% (95% CI 50.7-73.6). In Cohort 2, the BORR and BCRR were 93.5% (95% CI 90.0-96.1) and 69.8% (95% CI 64.0-75.1), respectively. In Cohort 3, the BORR was 78.0% (95% CI 69.7-84.8) and the BCRR was 50.4% (95% CI 41.4-59.4). Among the 801 patients included in the safety analysis set, treatment-emergent adverse events (TEAEs) were reported in 85.4% of patients, with grade≥3 TEAEs occurred in 48.4%. Grade≥2 peripheral neuropathy was observed in 0.7% of cases. Serious adverse events occurred in 17.9% of patients. 67.3% of patients reported Pola related TEAEs. Conclusion: This represents the largest real-world study of Pola to date. In real-world settings featuring greater heterogeneity among DLBCL patients, Pola-based regimens demonstrated promising clinical activity and were well tolerated. These findings offer valuable insights into treatment consideration, with additional evidence expected from continued follow-up and analysis of the POLAREAL study.