Statin Use May Improve Survival in Newly Diagnosed Multiple Myeloma Patients

Newly diagnosed multiple myeloma patients who are using statins have lower mortality rates than those who don’t, a large population-based cohort study reported.

In the study, “Statins Are Associated With Reduced Mortality in Multiple Myeloma,” published in the Journal of Clinical Oncology, researchers at St. Louis Veterans Health Administration Medical Center found that statin use can decrease both all-cause mortality and multiple myeloma-specific mortality.

Statins are widely used to treat people with high cholesterol and to prevent cardiovascular disease. They work by inhibiting HMG-CoA reductase, an enzyme that is involved in the lipid metabolism, particularly in the mevalonate pathway.

Because some multiple myeloma therapies also target the mevalonate pathway, researchers believe that statins may improve treatment outcomes in these patients. Indeed, previous studies have already demonstrated that statin therapy can accelerate myeloma cell death and prevent their proliferation. One such study, a randomized clinical trial of Mevacor (lovastatin) in multiple myeloma patients, showed improved progression-free survival in treated patients, but the study was too small (91 patients) to be conclusive.

In this study, researchers again addressed whether statin therapy could indeed improve outcomes for multiple myeloma patients. They used the Veteran Administration Central Cancer Registry to identify myeloma patients diagnosed between 1999 and 2013. Among the 4,957 such patients identified, 2,294 had been given statins.

Statin treatment was defined as having a statin prescription within three months prior to myeloma diagnosis, or any time after. Statins considered in the study included Lipitor (atorvastatin), Lescol (fluvastatin), Mevacor, Livalo (pitavastatin), Pravachol (pravastatin), Crestor (rosuvastatin), and Zocor (simvastatin).

Following a median follow-up of 34 months for statin users and 26 months for nonusers, 3,284 patients had died, including 1,415 people reported to also be statin users. In addition to having co-occurrence of more diseases, such as ischemic heart disease or diabetes, those in the statin group were also more likely to be white, have higher BMI, be of older age, have been diagnosed after 2006, and have differences in baseline hemoglobin and albumin levels.

Results revealed that statin users had higher median overall survival (39.5 months) compared to nonusers (27 months). After adjusting for potential confounders, the researchers reported a 21 percent decrease in all-cause mortality, and a 24 percent decrease in myeloma-specific mortality, among statin users compared with nonusers.

Several factors were found to be specifically associated with all-cause mortality and with myeloma-specific mortality. Those associated with increased mortality included older age, low BMI (below than 18.5 kg/m²), co-occurrence of more diseases, low hemoglobin levels (below 10 g/dL), low estimated glomerular filtration rate (below 30 mL/min/1.73 m²), and treatment with Aredia (pamidronate), a drug used for bone metastasis or lesions.

In contrast, autologous stem cell transplantation, black race, and higher BMI (25 kg/m² or more), were all associated with a reduced risk of both all-cause mortality and myeloma-specific mortality.

The researchers then stratified their data on the basis of race. Results still revealed an association between statin use and improved survival, both in black and white patients, which appeared to increase with the duration of statin therapy. Black patients appeared to benefit more from statin treatment than white patients, showing a higher reduction in both all-cause mortality (27% vs. 17%) and myeloma-specific mortality (33% vs. 19%).

Consistent with previous findings reporting a role for statins in stimulating bone formation, the researchers also found that these drugs decreased the risk for skeletal-related events by 31 percent.

Although the researchers acknowledge that patients may have been misclassified regarding statin use due to noncompliance, and that unmeasured confounding factors may have existed between statin users and nonusers, the findings still point to a marked benefit of statins in multiple myeloma patients.

“Our findings suggest a potential role for statin therapy in patients with MM,” Kristen Marie Sanfilippo, MD, MPHS, assistant professor in the department of medicine, hematology division at Washington University School of Medicine, and colleagues wrote. “The putative benefit of statin therapy in MM should be corroborated in a prospective study.”