Statin use is associated with improved survival in multiple myeloma: A Swedish population‐based study of 4315 patients

Abstract

Statin use has been associated with reduced cancer‐specific mortality among patients with several cancer types, including multiple myeloma (MM). We aimed to further elucidate the association of statin use and dose intensity with MM survival. Using Swedish population‐based national health registers, we identified all incident MM diagnoses occurring January 1, 2007 to December 31, 2013 and their drug dispensations and comorbidities. We assessed statin exposure in 6‐month periods pre‐ and post‐diagnosis, treated diagnosis as baseline for calculating survival time, and calculated hazard ratios (HR) and 95% confidence intervals (CI) of exposure‐related MM‐specific and all‐cause mortality using Cox regression. We assessed statin exposure during the entire follow‐up and risk of MM‐specific mortality in a nested case‐control analysis. We classified dose intensity according to American College of Cardiology/American Heart Association recommendations. We ascertained 4315 MM cases during follow‐up. Statin use was associated with reduced MM‐specific mortality (pre‐diagnosis use multivariate‐adjusted HR, 95% CI: 0.83, 0.71‐0.96; 6 months post‐diagnosis: 0.73, 0.60‐0.89; entire follow‐up: 0.65, 0.52‐0.80) and (more weakly) with all‐cause mortality. Intensity analyses suggested a dose‐response; MM‐specific mortality decreased with increasing statin intensity in all time windows (eg, 6 months post‐diagnosis: low [0.76 (0.56‐1.03)], medium [0.73 (0.58‐0.92)], high [0.33 (0.08‐1.32)] intensity). However, relatively few patients received high intensity treatment, and the trend was statistically significant only for unadjusted pre‐diagnosis use.In this large population‐based MM cohort, statin use was associated with improved MM‐specific survival in both sexes. Randomized prospective studies are warranted to evaluate statins as adjuvant treatment in MM.

The mevalonate pathway is an actionable vulnerability of t(4;14)-positive multiple myeloma

“…We, and others, have demonstrated that statins induce apoptosis in a subset of MM cell lines by directly inhibiting HMGCR, indicating that some MM cells are dependent on the MVA pathway for survival [8][9][10][11]. These preclinical data are supported by recent retrospective analyses, where statin use was associated with reduced MMspecific mortality [12,13]. Moreover, phase I/II trials in patients with relapsed/refractory MM have reported promising responses when a statin was combined with standard-of-care therapies in some, but not all, patients [14,15].…”

Lipid metabolism and cancer

“…Some inconsistent results were reported. Retrospective studies showed that statin treatment prolonged the survival of patients with multiple myeloma, colorectal cancer, and metastatic pancreatic cancer cotreated with first-line chemotherapy ( Abdel-Rahman, 2019 ; Brånvall et al, 2020 ; Cardwell et al, 2014 ). In contrast, randomized phase III trials in patients with SCLC, metastatic colorectal cancer, HCC, or gastric cancer showed that addition of pravastatin or simvastatin to standard chemotherapy offers no additional benefit ( Jouve et al, 2019 ; Kim et al, 2014 ; Lim et al, 2015 ; Seckl et al, 2017 ).…”

Cholesterol Metabolic Reprogramming in Cancer and Its Pharmacological Modulation as Therapeutic Strategy

“…Farooqui reviewed different randomized controlled trials and concluded that the addition of statins to standard chemotherapy is not able to enhance the survival in patients with advanced cancers and a prognosis of less than 2 years ( 195 ). A Swedish study, instead, concluded that statins use for 6 months in patients with multiple myeloma enhanced the survival rate of both men and women ( 196 ). In another study, atorvastatin was administered in patients with prostate cancer for 27 days before prostatectomy.…”