The Impact of Relative Dose Intensity of Rituximab-CHOP on Survival in Diffuse Large B-Cell Lymphoma Patients
Authors: Terada Yoshiki , Nakamae Hirohisa , Moriguchi Ran , Kanashima Hiroshi , Sakamoto Erina , Momose Dai , Aimoto Mizuki , Okamoto Shuichirou , Wada Eri , Koh Hideo , Nakane Takahiko , Takeoka Yasunobu , Koh Ki- Ryang , Yamane Takahisa , Nakao Yoshitaka , Ohta Kensuke , Mugitani Atsuko , Teshima Hirofumi , Hino Masayuki 
Published: April 2020

Abstract
Background. Recently several retrospective studies showed that relative dose intensity (RDI) in combination chemotherapy including CHOP significantly influences survival in aggressive lymphoma. Based on these data, maintaining high RDI in chemotherapy by, for example, prophylactic granulocyte colony-stimulating factor (G-CSF) administration has been attempted to obtain better outcome. Moreover, rituximab, a chimeric monoclonal anti CD20 antibody combined with CHOP chemotherapy (R-CHOP) has significantly ameliorated the outcome in patients with diffuse large B-cell lymphoma (DLBL). However, it is unclear if higher RDI even in combination with rituximab will improve outcome in B cell type aggressive lymphoma. Hence, in the current study, we retrospectively analyzed the impact of RDI in R-CHOP as an initial treatment on survival of patients with DLBL. Furthermore, we determined the factors influencing RDI.
Patients and Methods. We studied 100 previously untreated DLBL patients who underwent more than 3 courses of R-CHOP chemotherapies at 5 institutions from December 2003 to February 2008. The median age of the patients was 60 years old (range 19–79). The median number of R-CHOP course was 6 (range, 3–8). In the current study, the RDI was calculated by averaging the delivered RDIs of cyclophosphamide (CY) and adriamycin (ADR) for all chemotherapy courses.
Results. The median average RDI of CY and ADR (CY/ADR-RDI) in all patients was 87.9%. Twenty three of 100 patients were treated with RDI less than 75 %. With a median follow-up of 21.2 months, the probability of 4-year overall survival (OS) was significantly higher in patients with higher RDI (&gt;=75%) than that in patients with lower RDI (&lt;75%) (78.6 % vs. 60%; P = 0.01). In univariate Cox regression model to identify prognostic factors for OS, RDI [hazard ratio (HR) = 0.7 per 0.1 of RDI; 95% CI 0.6– 0.9; P = 0.02] and high/high-intermediate International Prognostic Index (IPI) (HR = 4.7; 95% CI 1.3–17; P = 0.04) were significant factors influencing OS. In multivariate model, RDI was only a significant factor influencing OS (HR = 0.8 per 0.1 of RDI; 95% CI 0.6–1.0; P = 0.04). In multivariate logistic analysis to determine factors influencing RDI, elderly patients (&gt;=51 ) [odds ratio (OR) = 0.2; 95% CI 0.1–0.7; P = 0.01] and high/high-intermediate IPI (OR = 0.3; 95% CI 0.1–1.0; P = 0.04) were significant factors for reduced RDI, whereas prophylactic G-CSF (OR = 3.2; 95% CI 1.1–9.3; P = 0.04) was found to be a significant factor for increased RDI.
Conclusion. In newly diagnosed DLBL patients, the current results demonstrated that high RDI in CHOP even when combined with rituximab was significantly associated with better survival and higher RDI could be effectively maintained by G-CSF.