Statin Therapy Improves Multiple Myeloma (MM) Specific Surviva

Background: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for treatment of dyslipidemia and prevention of coronary heart disease. Recently, a multicenter clinical trial found discontinuation of statin therapy in patients with estimated survival of < 1 year had no significant impact on mortality or cardiovascular outcomes [Kutner JAMA Int Med 2015]. In this trial, approximately 50% of patients had cancer as their primary diagnosis. However, statin use has been associated with improved cancer-specific survival in several malignancies. Preclinical evidence suggests that this effect may be independent of the lipid lowering properties. In addition, in the case of MM, statins influence similar pathways as the bisphosphonates. To understand the putative benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of MM patients.

Methods: We identified patients diagnosed with MM in the Veterans Administration Cancer Registry from September 1, 1999 to December 31, 2009 and followed them through October 2014. We excluded patients who did not receive MM directed therapy within 6 months of diagnosis or who died within 6 months of diagnosis. We defined statin use as the presence of any prescription for a statin on or after the date of MM diagnosis. To standardize statin utilization, we calculated the defined daily dose (DDD), which allows normalization of dose and potency amongst differing statins. The DDD is the assumed average maintenance dose per day for a drug used for its main indication. To reduce immortal time bias, we assessed statin use as a time varying covariate. Cox proportional hazards regression modeling assessed the association between statin use, overall mortality, and cause-specific mortality, while controlling for known MM prognostic factors. Propensity score analyses balanced baseline differences between statin users and non-users.

Results: The cohort included a total of 3,069 patients, of whom 1,334 received statin therapy. Statin use was associated with a significant decrease in all-cause mortality (adjusted HR (aHR) 0.81, 95% CI: 0.73-0.90). Stratifying statin use by DDD, MM patients receiving <365 days of statins had a 14% reduction in all-cause mortality (aHR 0.86, 95%: CI 0.76-0.97), while patients receiving ≥365 days of statin therapy had a 24% reduction in mortality (aHR 0.76; 95% CI: 0.66-0.87). When looking at MM-specific mortality, statin use was associated with a 19% reduction in death from MM (aHR 0.81, 95% CI: 0.71-0.93). Stratifying statin use by DDD, we found that patients receiving <365 days of statin use had a 15% reduction in MM-specific mortality (aHR 0.85, 95%: CI 0.72-0.99), while patients receiving ≥365 days of statin therapy had a 25% reduction in mortality (aHR 0.75; 95% CI: 0.62-0.91). At baseline, statin users were more likely to be older, obese, Caucasian, and have more medical comorbidities (diabetes, chronic kidney disease, ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and dyslipidemia). These differences were well balanced in the propensity score analysis, in which statin use remained significantly associated with a reduction in mortality (aHR 0.60; 95% CI: 0.52-0.70).

Conclusion: In this cohort of patients with MM, statin therapy was significantly associated with a reduction in both all-cause and MM-specific mortality. These findings argue against discontinuing statin therapy in patients with MM, including those with a prognosis of < 1 year.