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.