title: Statin use has negative clinical impact on non-germinal center in patients with diffuse large B cell lymphoma in rituximab era.
abstract: Rituximab improved prognosis in diffuse large B cell lymphoma (DLBCL). However, activity of rituximab may be reduced by conformational change in CD20 by statin-induced cholesterol depletion. Conformation change in CD20 could impair the binding of rituximab and significantly decrease the killing effect of lymphoma cells. R-CHOP therapy could counteract the prognostic gap between GC type and non-GC type. We investigated whether statin use could have different clinical impacts on immunohistochemical DLBCL subtypes in the rituximab era. We analyzed data from 409 patients with de novo DLBCL who received R-CHOP therapy. During median follow-up time of 38.6 months, 3-year progression-free survival (PFS) and overall survival (OS) in the GC type were similar to those in the non-GC type (PFS, p=0.125; OS, p=0.201). Moreover, survivals were comparable between patients with statin therapy and those without the statin therapy (PFS, p=0.282; OS, p=0.273). We also analyzed whether statin therapy would have clinical significance by immunophenotypes in patients treated with R-CHOP therapy. The non-GC type with statin therapy had inferior PFS and OS compared to other groups (PFS, p=0.008; OS, p=0.006). In multivariate analysis, statin therapy had significant negative impacts on survivals of the non-GC type independent of other clinical factors (PFS, hazard ratio/HR: 1.553, 95% CI: 1.058-2.279, p=0.024; OS, HR=1.532, 95% CI: 1.041-2.255, p=0.023). Therefore, statin therapy negatively affected the clinical outcome of the non-GC phenotype, but it was beneficial to R-CHOP therapy in DLBCL.
authors.affiliation: Department of Hematology-Oncology, Pusan National University Hospital Medical Research Institute, Busan, Republic of Korea.
authors.forename: Moo-Kon
authors.initials: MK
authors.lastname: Song
authors.affiliation: Department of Hematology-Oncology, Pusan National University Hospital Medical Research Institute, Busan, Republic of Korea. Electronic address: Hemon@pusan.ac.kr.
authors.forename: Joo-Seop
authors.initials: JS
authors.lastname: Chung
authors.affiliation: Department of Hematology, Gyeong-Sang National University Hospital, School of Medicine, Gyeong-Sang National University, Jinju, Republic of Korea.
authors.forename: Gyeong-Won
authors.initials: GW
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
authors.forename: Su-Hee
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Department of Hematology, Gachon University Gil Medical Center, Incheon, Republic of Korea.
authors.forename: Junshik
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Hematology, Korea Cancer Center Hospital, Seoul, Republic of Korea.
authors.forename: Dong-Yeop
authors.initials: DY
authors.lastname: Shin
authors.affiliation: Department of Hematology-Oncology, Pusan National University Hospital Medical Research Institute, Busan, Republic of Korea.
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Diffuse large B cell lymphoma; Germinal center; Rituximab; Statin