Prognostic Impact of Six Versus Eight Cycles of Standard Regimen in Patients With Diffuse Large B-Cell Lymphoma

Background: R-CHOP-21 has been the standard treatment for diffuse large B-cell lymphoma (DLBCL), but no randomized trials have focused on the number of cycles of regimens. This study was designed to assess the effectiveness of six cycles of standard regimens for DLBCL compared with eight cycles in terms of prognostic impact, considering confounding by relative dose intensity (RDI).  Methods: A total of 685 patients newly diagnosed with DLBCL were identified within the database of three participating institutions from 2007 to 2017. Patients treated using six cycles of standard regimens were matched by propensity scores with those treated using eight cycles. Overall survival (OS) was compared using Cox hazard modeling with restricted cubic spline (RCS).  Findings: After matching, 138 patients treated using six cycles were compared with 138 patients treated using eight cycles. Eight cycles did not significantly improve OS in the Cox hazard proportional model (P = 0·608, 95% confidence interval 0·453–1·588, hazard ratio 0·849). RCS-Cox models confirmed that the number of cycles interacted with neither effect of RDI on OS, nor effect of age on OS. Eight cycles of regimens had little impact on OS compared with six cycles in any category divided by International Prognostic Index. Sensitivity analyses strengthened the robustness of no evidence of any difference in outcome for six cycles compared with eight cycles.  Interpretation: Even considering the impact of RDI, six cycles of the standard regimen for DLBCL is not inferior to eight cycles.  Funding Statement: None. Declaration of Interests: TY has received research funds and honoraria from Stargen, Boehringer Ingelheim, Mundipharma, Solasia, Pfizer, and Chugai Pharmaceutical. All other authors declare no competing interests. Ethics Approval Statement: This study was conducted in accordance with the principles of the Declaration of Helsinki, and all protocols were approved by the appropriate institutional review boards. The need to obtain written, informed consent was waived, since this study used retrospective data obtained only from hospital medical records.