Differential Impact of Relative Dose-Intensity Reductions in Diffuse Large B-Cell Lymphoma Treated with R-CHOP21 or R-CHOP14

Abstract

DLBCL is an aggressive lymphoma treated with R-CHOP. Recently, attempts have been made to improve the outcome by increasing both dose-density and intensity but there have been no benefits in terms of survival. When treating malignancies RDI is important to consider but there is little published information on DLBCL. The purpose of this study was to analyze the differential prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14. From January 2001 to August 2013 we included DLBCL patients homogenously treated with R-CHOP21 or R-CHOP14, with or without radiotherapy, at University Hospital Son Espases, Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona (N = 157). In order to avoid selection bias the patients were retrospectively identified from the Pathology Department and Pharmacy registries. Median follow-up was 68 months. There was no difference in the response or survival between the two cohorts. In the R-CHOP21 group, both a reduction higher than 15% in RDI (RR 7.41) and R-IPI (RR 2.99) were independently associated with OS. However, a reduction higher than 15% in RDI (RR 4.41) was only noted for PFS. In the R-CHOP14 group, NCCN-IPI (RR 7.09) and B-symptoms (RR 5.37) for OS; AA stage III-IV (RR 6.26) and bulky disease (RR 4.05) for PFS. There was a trend towards a higher rate of RDI reduction observed in the R-CHOP14 group but it only made an impact in the R-CHOP21 group. We conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival, but only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions.

Relative dose intensity of R‐CHOP therapy and patient outcomes in advanced follicular lymphoma

“…To the best of our knowledge, this is the first report to evaluate between RDI and the clinical outcome in patients with advanced‐stage FL treated R‐CHOP. Several studies have found a correlation between the RDI of R‐CHOP and the clinical outcomes of diffuse large B‐cell lymphoma . However, in this study, we found no significant impact of RDI on patient outcomes in advanced‐stage FL.…”

“…Several studies have found a correlation between the RDI of R-CHOP and the clinical outcomes of diffuse large B-cell lymphoma. [10][11][12][13] However, in this study, we found no significant impact explanation is that patients with low tumor burden (who might be candidates for "watch and wait" strategy) were included.…”

Impact of Pretreatment Neutrophil Count on Chemotherapy Administration and Toxicity in Dogs with Lymphoma Treated with CHOP Chemotherapy

“…To characterize modifications of chemotherapy schemes, the concept of RDI, which reflects delivered DI divided by standard DI, has been introduced . A decrease in RDI in human patients with diffuse large B‐cell lymphoma who are treated with rituximab‐CHOP (R‐CHOP) is associated with poorer outcome . In 1 study in which dogs with lymphoma were treated with multidrug chemotherapy and half‐body irradiation, development of grade III or IV neutropenia was positively associated with remission duration, but RDI was not associated with outcome .…”

Impact of doxorubicin dose capping on the outcome of DLBCL patients with elevated body surface area

“…Lipocalin-2 from both myeloid cells and the epithelium combats Klebsiella pneumoniae lung infection in mice Elisabeth P. Cramer, 1 Sara L. Dahl, 1 Björn Rozell, 2 Kasper J. Knudsen, 3,4 Kim Thomsen, 5 Claus Moser, 5 Jack B. Cowland, 1,6 Lipocalin-2 is a eukaryotic siderophore-binding protein that prevents the growth and spread of microorganisms that require siderophoremediated uptake of soluble iron. 1 Consequently, lipocalin-2 knockout mice (Lcn2 2/2 mice) are more susceptible to infection with the siderophore-producing pathogen Klebsiella pneumoniae 2 than wildtype (WT) mice.…”

“…DLBCL is a curable disease in which relative dose intensity has been described to be associated with treatment efficacy. 2 However, clinicians may be concerned with the toxicity of high doses of anthracyclines in patients with elevated BSA.…”