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

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
• statins
• patient survival
• chemosensitivity

Disclosure statement

PS reports research support from AstraZeneca and serves as a consultant for Genentech-Roche. F.V. receives research funding from CRISP Therapeutics and Geron Corporation and received in the last 3 years honoraria from i3Health, Elsevier, America Registry of Pathology, Congressionally Directed Medical Research Program, and the Society of Hematology Oncology.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [NKA], upon reasonable request.

Additional information

Funding

This research is supported in part by The University of Texas MD Anderson Cancer Center Support Grant from National Institutes of Health [P30 CA016672]. PS salary is supported by the Lymphoma Research Foundation (Career Development Award) https://lymphoma.org/news/meet-the-2020-career-development-award-and-postdoctoral-fellowship-grantees/.