Statins enhance the chemosensitivity of R-CHOP in diffuse large B-cell lymphoma

Leuk Lymphoma. 2022 Jun;63(6):1302-1313. doi: 10.1080/10428194.2021.2020782. Epub 2021 Dec 31.

Abstract

The beneficial effect of statins on the anti-lymphoma activity of the rituximab-based chemotherapy regimen is controversial. Here, we retrospectively reviewed patients with naïve-treated advanced diffuse large B-cell lymphoma (DLBCL) receiving frontline R-CHOP, and for whom data regarding differential statins use was available at the time of initiation of treatment. We observe that patients treated with statins and R-CHOP experienced a significantly higher CR rate as compared to those who received R-CHOP only. We further show that patients receiving medium or high intensity statins and R-CHOP experienced a significantly higher CR as compared to those treated with R-CHOP. Six-year progression free survival was higher for patients who received medium or higher intensity statins as compared to low or no statins. The potential contribution of cholesterol pathway in doxorubicin sensitivity was supported by in vitro/in vivo studies. Our study suggests that targeting cholesterol-using lovastatin could be a therapeutic strategy to enhance responses to R-CHOP in DLBCL patients.

Keywords: DLBCL; R-CHOP; chemosensitivity; patient survival; statins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Lymphoma, Large B-Cell, Diffuse*
  • Prednisone / therapeutic use
  • Retrospective Studies
  • Rituximab / therapeutic use
  • Treatment Outcome
  • Vincristine / adverse effects

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone