Pola-R-CHP in newly diagnosed primary mediastinal B-cell lymphoma:high efficacy and tolerability

Abstract Introduction Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) that predominantly occurs in young adults and presents with bulky mediastinal mass. In the rituximab era, dose-dense regimens are recommended for newly-diagnosed PMBCL, with concerns regarding long-term toxicities. Single agent of polatuzumab vedotin (Pola) was proved to significantly induce cytotoxicity against PMBCL in vitro, while this population was excluded in the POLARIX trial, the landmark study which changes the frontline DLBCL treatment landscape. ObjectiveTo determine the safety and efficacy of first-line Pola-R-CHP regimen in patients with newly-diagnosed PMBCL. MethodsFrom September 2023 to December 2024, patients with previously untreated PMBCL that received Pola-R-CHP regimen were enrolled in this study, adhering to the same dosage and schedule as outlined in the POLARIX trial. Positron emission tomography/computed tomography (PET/CT) scans were conducted at baseline, following three cycles (Interim) and six cycles (End of Treatment, EoT) of therapy. Treatment response was assessed utilizing the 2014 Lugano response criteria. Adverse events (AEs) were classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. ResultsA total of 14 PMBCL patients received Pola-R-CHP as initial treatment. The median age was 32 years (range, 17-51) and there was a female predominance (64.3%). 64.3% of patients exhibited bulky diseases, 50% presented with B symptoms, and 71.4% had elevated LDH. Most patients had limited-stage disease (Ann Arbor I–II, 92.9%), good performance status (ECOG 0-1, 92.9%), and low-risk aaIPI scores (0–1, 85.7%). Pleural and pericardial effusions were detected in 28.6% and 42.9% of patients, respectively. Over a median follow-up of 13.1 months (range, 6.0-21.5), all patients completed 6 cycles of Pola-R-CHP, achieving an objective response rate (ORR) of 100%. Interim PET/CT showed a partial metabolic response (PMR) in 64.3% and complete metabolic response (CMR) in 35.7% of patients. Upon completion of the Pola-R-CHP treatment, CMR rate increased to 92.9%. 8 patients with PMR at interim improved to CMR at EoT, with only 1 patient remaining in PMR. Throughout the follow-up period, no progression or deaths occurred. The safety profile was favorable and manageable. Treatment was well-tolerated with no discontinuations due to AEs. The most common grade 3–4 AEs were neutropenia (42.9%, resolved with G-CSF) and vomiting (14.3%). ConclusionsOur research fills the evidence gap in the POLARIX trial by providing real-world experience for the use of Pola-R-CHP as an upfront treatment in PMBCL, which demonstrates promising trends towards sustained response with acceptable safety profile. These findings necessitate further validation in future trials.