Abstract
Diffuse large B-cell lymphoma (DLBCL) predominantly affects older adults, with an increasing proportion of patients aged ≥ 80 years. Although the POLARIX trial demonstrated improved progression-free survival with polatuzumab vedotin (Pola) combined with R-CHP (Pola-R-CHP), its applicability to very elderly patients remains unclear. A multicenter, retrospective, cohort study was conducted at seven hospitals in Japan, enrolling 172 previously untreated DLBCL patients who initiated Pola-R-CHP between August 1, 2022 and May 1, 2024. Patients were stratified by age (< 80 vs. ≥80 years). Initial dose intensity (IDI), average relative dose intensity (ARDI), treatment efficacy, and safety outcomes were evaluated. In patients aged ≥ 80 years (n = 44), the overall response rate (ORR) was 89.5%, comparable to the 97.3% in patients aged < 80 years. However, treatment-related mortality (TRM) was higher in the older group (11.4% vs. 2.3%). In this cohort, median IDI and ARDI for doxorubicin and cyclophosphamide were markedly lower, whereas Pola dosing was relatively preserved. Higher Pola IDI was associated with an increased incidence of severe adverse events (sAEs), and a lower Geriatric Nutritional Risk Index (GNRI) was independently correlated with both reduced ORR and increased sAEs. Pola-R-CHP demonstrates promising efficacy in DLBCL patients aged ≥ 80 years. However, the increased TRM highlights the importance of cautious toxicity management. Individualized dose modifications, particularly for cytotoxic agents, and comprehensive nutritional assessments may improve treatment tolerability and outcomes in this vulnerable population.