First-line Polatuzumab vedotin plus R-CHP in primary mediastinal B-cell lymphoma: A real-world study bridging the gap of the POLARIX trial.

[UNLABELLED] Objective primary mediastinal B-cell lymphoma (PMBCL) is a distinct, aggressive lymphoma predominantly affecting young adults. While dose-intensive regimens are often recommended, their associated long-term toxicities and the necessity of consolidative radiotherapy remain major concerns. Given that PMBCL was explicitly excluded from the landmark POLARIX trial, we sought to evaluate the real-world efficacy and safety of first-line Pola-R-CHP in this specific population. Methods this single-center study analyzed 16 consecutive patients with newly diagnosed PMBCL treated with six cycles of Pola-R-CHP between September 2023 and June 2025. Efficacy was assessed via PET/CT (Lugano 2014 criteria) and safety via NCI-CTCAE v5.0. Results the median age was 30 years, with a female predominance (62.5%). Bulky disease was present in 62.5% of patients, and 87.5% had low-risk aaIPI scores. All patients completed six cycles of Pola-R-CHP treatment, achieving an objective response rate of 100%. The end-of-treatment complete metabolic response rate was 93.8%, with profound response deepening observed between interim and final assessments. After a median follow-up of 16.4 months, no relapses or deaths occurred, with all patients remaining in sustained remission. The most common grade 3–4 adverse event was neutropenia (43.8%). Pola-related peripheral neuropathy was predominantly low-grade (56.3% grade 1–2). Conclusion our findings provide the first preliminary clinical evidence that Pola-R-CHP is a highly effective and well-tolerated frontline strategy for PMBCL in this real-world cohort, which warrants further validation in larger, multicenter studies.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s00277-026-07024-x.