Statins Linked to Improved Survival in Patients With CLL/SLL
Statin use in CLL/SLL patients showed improved survival regardless of treatment, suggesting repurposing potential for this accessible drug.
In the first large-scale analysis to specifically investigate the use of statins in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), researchers identified that the use of statins was associated with improved overall survival and cancer-specific survival, regardless of patient demographics.
While more studies are needed to confirm these findings, Ahmad Abuhelwa, MD, lead investigator, is hopeful, especially considering that statins are an accessible, safe, and inexpensive drugs.
“These findings, I think, open the door for further research into drug repurposing as a cost-effective strategy to improve on cancer outcomes. We have known statins for many years, so if we can confirm that they are beneficial, then that would hold a great promise for optimizing treatments without the long timelines and any costs associated with developing new drugs,” said Abuhelwa, assistant professor of clinical pharmacology and pharmacometrics at the University of Sharjah, United Arab Emirates, in an interview with Targeted OncologyTM.
In the interview, Abuhelwa delved into this research and its significance for the CLL/SLL field.
Targeted OncologyTM: What prompted this line of research?
Ahmad Abuhelwa, MD
Abuhelwa: [Patients with cancer] usually have comorbidities and are taking concomitant medications along with their cancer treatments. But patients do not know whether these concomitant medications might affect the cancer treatment itself. CLL and SLL are predominantly diagnosed in older adults. Many patients in their 60s [and older] have comorbidities [and] cardiovascular risk factors, and they are prescribed drugs.
There has been some literature with regards to potential anticancer properties for statins, but [in this study] we have done this analysis that provides strong clinical evidence in patients receiving contemporary treatment regimens with targeted therapists like ibrutinib [Imbruvica]. That was the prompt for doing the research. To the best of our knowledge, this was the largest pooled analysis to date evaluating the association between statin use and survival outcomes in this patient population, and we have analyzed data from 4 randomized clinical trials, and we have observed that patients who were using statin at the start of their cancer treatment had significantly bettered survival outcomes.
Do you have a hypothesis as to what might be behind these outcomes?
Statins are used to lower cholesterol levels. Beyond lowering cholesterol, they are also known to have anti-inflammatory, antiangiogenic and immune-modulating effects, and they have been shown in the lab studies to disrupt cancer survival pathways and induce death of cancer cells. Particularly here with CLL cells, they rely on lipid metabolism. To the mechanism of action of these drugs, they inhibit an enzyme called HMG-CoA reductase. That enzyme is responsible for the synthesis of cholesterol. Now, it has been shown that cells, hematological cancer cells, including CLL cells, they have 20 times the level for this enzyme, the HMG-CoA reductase enzyme, and that might suggest a potential mechanism for their cytotoxic effects, because they inhibit that enzyme.
In this study, we did not directly study the mechanism, but our findings support the possibility that statins might have a disease-modifying effects in CLL/SLL, but this needs to be further explored in the lab as well as in prospective clinic trials.
What do you see as the next line of research in this area?
We have seen a strong link between statin use and better survival for patients, so that is promising, but we cannot recommend statin for cancer prevention or treatment based on this study alone. Further clinical trials are needed to determine if statin have a direct effect or a direct benefit on cancer. Given that statins are affordable and widely available, if future research confirms their benefit, and then statin could become an easy and cost-effective way to improve survival in patients with CLL/SLL.
What is the significance of this study?
One of the interesting things in terms of significance of this study is that it showed a significant reduction, a 61% reduction in the risk of cancer-specific death, and that reflects mortality from cancer itself. This is in addition to a 38% reduction in the risk of death from any cause and a 26% reduction in the risk of disease progression. All these effects were irrespective of the patient’s age, sex, weight, physical functioning, disease severity, length of time since their diagnosis, comorbidities, or the use of other cardiovascular medications.
Also, our analysis showed that statin use was not associated with an increase in the risk of severe [adverse events] or toxicities. As drugs, statins are generally well tolerated. Common [adverse events] might include mild muscle pain or liver enzyme elevation, but these are infrequent, and they are manageable.
These findings, I think, open the door for further research into drug repurposing as a cost-effective strategy to improve on cancer outcomes. We have known statins for many years, so if we can confirm that they are beneficial, then that would hold a great promise for optimizing treatments without the long timelines and any costs associated with developing new drugs.
Is there any other research being done around drug repurposing in oncology?
We also looked at other concomitant medications like [proton pump inhibitors (PPIs)]. They inhibit the secretion of acid. We have shown in other research that patients who take PPIs have reduced benefits from immunotherapy. The pH is one thing, but there is also a lot of literature that demonstrate that they can affect the gut microbiota, and they have a complex interaction with the immune system. They can mediate the immune system in a negative way. But here we have it in a positive way with statins. I think that is interesting in the sense that [patients with cancer], on average, they take 7 other medications to treat comorbidities or [adverse] effects because of the cancer treatment. They are often worried if these drugs going to harm the cancer treatment. I think in that sense, they deserve answers.
