• CPOP-R is an active regimen in first-line therapy of patients with first-line DLBCL. • Non-inferiority of CPOP-R to CHOP-R, with respect to the CR/CRu rate, could not be demonstrated because of the decrease in the planned number of enrolled patients. • Differences in non-disease related comorbid factors rather than lack of efficacy appeared responsible for the disparity in deaths between study arms. The 2-year survival rate of 74% for patients on CPOP-R is consistent with historical experiences in high-risk patients. 5 • CPOP-R was significantly less cardiotoxic than CHOP-R as evidenced by the significant reduction in the number of patients with any cardiac toxic event (8.5% vs 36.5%), severe LVEF declines (0.9% vs 8.3%), or CHF (0% vs 6.3%) or by the number of patients with increase over baseline in troponin T levels (8.5% vs 34.5%). • Larger studies are required to establish the potential role of the CPOP-R regimen as