Exploring an independent association between rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone dose intensity and clinical outcomes in large B-cell lymphoma: Analyses of subsequent endpoints following a complete response in a real-world cohort of 1369 patients

Abstract

Introduction Rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) is a standard first-line treatment in large B-cell lymphoma (LBCL). Dose intensity is frequently reduced because of toxicity or concerns of tolerability. The true impact of such treatment modifications on the response rates is difficult to assess in nonrandomized comparisons because of complex and reciprocal interactions between various determinants of both variables. To avoid these confounding biases, this study was designed to analyze subsequent outcomes after a complete response is achieved with frontline therapy, aiming to uncover an independent link between R-CHOP dose-intensity and long-term outcomes in LBCL. Methods Patients treated between 2012 and 2024 were included. Reduced dose-intensity was predefined as more than 20% dose reduction for any one of the drugs for two cycles or a cumulative delay of >= 21 days. The primary and secondary objectives were the duration of complete response and the cumulative incidence of relapse (CIR), respectively. Results The LBCL cohort consisted of 1369 consecutive cases. For this study, 953 were eligible, with 728 and 225 patients in the dose-intense and reduced-intensity groups, respectively. Duration of complete response was significantly longer for the dose-intense group with a 3-year estimate of 87.8% vs 68.8% (hazard ratio: 0.39, p < .0001). The estimated 3-year cumulative incidence of relapse was 10.3% vs 21.4% (hazard ratio: 0.51, p = .004), favoring the dose-intense group. Reduced dose intensity was an independent risk factor on multivariate analysis for both endpoints. Conclusions Focusing on long-term outcomes after CR, this study demonstrates an increased risk of relapse when R-CHOP intensity is reduced, providing novel evidence that complements the association between reduced treatment intensity and inferior LBCL outcomes.