Dose-Attenuated-Polatuzumab Vedotine plus CHP vs. Dose-Attenuated -R-CHOP in Patients Aged ≥ 80 Years with Diffuse Large B-Cell Lymphoma: A Retrospective, Propensity Score-Matched Analysis Stratified by Simplified Frailty Score.

Background: Polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisolone (PRCHP) is a new standard first-line therapy; however, patients aged >80 years were excluded from the POLARIX trial. This single-center, retrospective study evaluated the efficacy and safety of dose-attenuated PRCHP compared with those of dose-attenuated RCHOP in very elderly patients. Methods: A total of 63 participants aged 80 years or older were treated with PRCHP, and 76 were treated with RCHOP. Propensity score matching (PSM) was performed to adjust for baseline differences in Ann Arbor stage, international prognosis index, and frailty score. Results: After a 1:1 PSM matching, 59 patient pairs were selected (median age: 84 years). Patients were classified as fit (n= 9, 15%), unfit (n= 21, 36%), or frail (n= 29, 49%) based on their frailty scores. The overall response rate, complete response rate, overall survival, and progression-free survival (PFS) at 12 months were comparable between the dose-attenuated PRCHP and RCHOP groups. In patients with frailty, the 12-month PFS was comparable (50.9% vs. 53.7%); however, in non-frail patients, the PFS was higher in the dose-attenuated PRCHP group than that in the RCHOP group (80.8% vs. 60.1%, p=0.04). Safety profile of grade 3/4 adverse events was similar for both groups; however, peripheral neuropathy was prominent in the RCHOP group (p=0.06). Conclusion: Despite limitations-including the retrospective design, single-center setting, small sample size, and heterogeneous dose modifications-this study suggests that dose-attenuated PRCHP offers comparable efficacy and safety to dose-attenuated RCHOP in patients aged >80 years. PFS may be prolonged in non-frail patients receiving PRCHP, with a potentially lower risk of peripheral neuropathy.