Authored by Brian Koffman, MDCM )retired), MSEd
Bottom Line:
Several studies have shown that statin use is associated with improved outcomes in CLL / SLL patients regardless of their CLL therapy.
Who Performed the Research and Where Was it Published:
The latest of many articles on statin use in chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL) was published by Dr. A.Y. Abuhelwa of the University of Sharjah, United Arab Emirates, and international colleagues, including Dr. Jennifer Brown in the medical journal, Blood Advance in April 2025.
Background:
As many CLL / SLL patients are older, statin use related to high cholesterol or heart disease is common. Past cancer studies, including CLL, have demonstrated an association of its use with lower overall cancer-related mortality. Perhaps this is due to its properties beyond its lipid-lowering capacity, such as its anti-neoplastic, anti-inflammatory, and immunomodulatory effects. Inflammatory cytokine (enzyme) synthesis may be reduced, and they may induce apoptosis (programmed cell death) of CLL cells. We know from our experience with BTK inhibitors how effectively blocking B cell receptor signaling controls CLL / SLL. Preclinical studies suggest that statins may similarly disrupt critical signaling pathways upregulated in CLL for cell survival and proliferation, leading to cell death. How statins control cancer is a fertile and ongoing area of research.
This retrospective data mining was done to explore the relationship between statin use and CLL outcomes, including overall survival (OS) and progression-free survival (PFS), in the era of modern targeted therapies such as ibrutinib. It was also designed to assess whether grade ≥3 or serious adverse events (AE) were increased in CLL patients.
Methods:
Individual patient data was pooled from four randomized, completed clinical trials that involved ibrutinib alone or in various combinations in at least one arm. The trials were exclusively for adults aged 18 years or older with CLL or SLL.
Results:
- Patient Population:
- There were 1,467 CLL / SLL patients in the four studies.
- 424 (29%) were on statins at baseline.
- The pooled cohort’s median follow-up time was five years for OS and just under two years for PFS.
- Patients on statins were:
- older,
- more commonly females,
- heavier,
- affected by worse performance status and a greater number of comorbidities
- The statins used across the cohort (n=424) included:
- simvastatin (n=149, 35%),
- rosuvastatin (n=69, 16%),
- atorvastatin (n=170, 40%),
- fluvastatin (n=2, <1%),
- pravastatin (n=25, 6%),
- lovastatin (n=9, 2%).
- Other cardiovascular drugs used at baseline included
- beta-blockers (328 patients, 22%),
- calcium channel blockers (193 patients, 13%),
- ACEI/ARBs (414 patients, 28%), and
- diuretics (246 patients, 17%)
- Outcomes:
- Statin use was significantly associated with improved OS, with a hazard ratio of HR [95%CI]: 0.68 and PFS 0.77. That means there was almost a one-third and one-quarter improvement in overall survival and progression-free survival, respectively.
- After adjusting for variables including patient’s diagnosis, age, sex, weight, performance status, bulky disease ≥ five cm., time since initial diagnosis, comorbidity count, and use of other cardiovascular drugs (beta-blockers, calcium channel blockers, ACEI/ARBs, diuretics), statin use remained significantly associated with improved OS and PFS.
- Baseline statin users exhibited a higher 2-year survival probability compared to non-users. The 2-year OS probability was 89% for statin users versus 82% for non-users.
- The 2-year PFS was 54% for statin users, compared to 46% for non-users, suggesting the statin may slow disease and time to first treatment.
- Importantly, there were no significant variations in PFS and OS between those treated with ibrutinib and those who were not, suggesting that statin use leads to improved survival outcomes across different therapies and patient types.
- Specifically, statin users had fewer deaths from disease progression. To be clear, the benefit of statin use was not solely the result of lower cardiac deaths.
- There was also no increased risk of Grade 3 or higher serious AEs in the statin group.
Discussion and Conclusions:
This retrospective analysis adds to prior research demonstrating that statin use at diagnosis was associated with slower CLL / SLL pretreatment disease progression. Prior preclinical work has also demonstrated how it may work synergistically with venetoclax. This publication shows statins broadly and meaningfully improve OS and PFS without increasing adverse events. This, of course, does not mean all CLL / SLL patients should start on a statin as they can be difficult to tolerate for some. Still, it does suggest if a statin is an option because of other indications, there is another good reason to add it to your treatment regimen.
Sources:
The source article summarized here can be read at: Statin use and survival in SLL/CLL treated with ibrutinib: Pooled analysis of four randomized controlled trials.
Other articles referenced are:
- Influence of Statin Therapy On the Clinical Course of Chronic Lymphocytic Leukemia
- Statins enhance efficacy of venetoclax in blood cancers
