Statins May Improve Survival Among Patients With CLL/SLL Receiving Ibrutinib

Using common cholesterol-lowering medications may improve certain blood cancer outcomes without compromising safety, a review of randomized controlled trials found.1

While previous research has pointed to an association between statin use and reduced risk of death for several cancer types, the connection has not previously been drawn between statin use and outcomes such as overall survival (OS) and progression-free survival (PFS) among patients receiving newer cancer treatments, such as ibrutinib, explained Ahmad Abuhelwa, PhD, the study’s principal investigator and assistant professor of pharmacy practice and pharmacotherapeutics at the University of Sharjah, in a press release outlining the findings.2

“This is the first systematic evaluation of the association of statin use with survival outcomes in patients with CLL or SLL who have been treated with contemporary targeted agents such as ibrutinib,” Abuhelwa said. “Our results highlight a strong link between statin use and improved survival in this patient population.”

Data from a collection of 4 randomized controlled trials found that using statins lowered the risk of cancer-related death by 61%. | image credit: Saiful52 - stock.adobe.com

Data from a collection of 4 randomized controlled trials found that using statins lowered the risk of cancer-related death—a primary end point of the study—by 61% (adjusted hazard ratio [aHR], 0.39; 0.22-0.70; P = .001) among patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) being treated with the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica; Pharmacyclics and Johnson & Johnson).1

Published in Blood Advances, the review included data from nearly 1500 patients included in the RESONATE (NCT01578707; assessing ibrutinib vs ofatumumab [Kesimpta; Novartis]), RESONATE-2 (NCT01722487; assessing ibrutinib vs chemotherapy [chlorambucil]), iLLUMINATE (NCT02264574; assessing ibrutinib plus obinutuzumab [Gazyva; Genentech] vs chemotherapy [chlorambucil]), and HELIOS (NCT01611090; assessing ibrutinib plus chemotherapy [bendamustine] and rituximab [Rituxan; Genentech and Biogen] vs chemotherapy and rituximab alone) trials.3-6

For the 29% (n = 424) of patients who were taking statins at the start of treatment, there was a 38% reduced risk of death (aHR for OS, 0.62; 0.48-0.79; P < .001) and a 24% reduced risk of disease progression or death (aHR for PFS, 0.74; 0.62-0.89; P = .001)—the study’s other 2 primary end points. Median follow-up time was 60.5 months for OS and 22 months for PFS.1

These results were seen regardless of various confounding factors, such as diagnosis, age, sex, weight, physical functioning, disease severity, time since diagnosis, comorbidities, use of other medications for heart conditions or blood pressure, and the treatment regimen they were receiving.

“These findings don’t allow us to say for certain that statins directly improve cancer outcomes,” Abuhelwa commented in the press release.2 “However, the fact that this association remained strong even after accounting for multiple factors makes it an important area for future research.”

The median age of patients in the trials was 65 years, and two-thirds (66%) were men.1 The majority (92%) of patients had CLL, while the remaining 8% had SLL. The researchers found no difference in results between CLL vs SLL diagnosis (OS P-interaction = 0.77; PFS P-interaction = 0.52).

The group also found no significant difference in statin use and grade 3 or higher side effects—a secondary end point of the review—even in the adjusted analysis (odds ratio, 0.92; 0.65-1.28).

Limitations of the review outlined by the researchers included it being an observational study and that the study did not determine the effect of specific statin types, doses, or duration on survival outcomes. The group highlighted the need for future research to validate their findings and to assess the underlying effect of statins in the disease.

References

1. Abuhelwa AY, Almansour SA, Brown JR, et al. Statin use and survival in SLL/CLL treated with ibrutinib: Pooled analysis of four randomized controlled trials. Blood Adv. Published online April 23, 2025. doi:10.1182/bloodadvances.2024015287
2. Statin use may improve survival in patients with some blood cancers. American Society of Hematology. Published online April 23, 2025. Accessed April 28, 2025. https://www.hematology.org/newsroom/press-releases/2025/statin-use-may-improve-survival-for-some-blood-cancers
3. Byrd JC, Brown JR, O’Brian S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. New Engl J Med. 2014;371:213-223. doi:10.1056/NEJMoa1400376
4. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. New Engl J Med. 2015;373:2425-2437. doi:10.1056/NEJMoa150938
5. Moreno C, Greil R, Dermirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2018;20(1):43-56. doi:10.1016/S1470-2045(18)30788-5
6. Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2016;17(2):200-211. doi:10.1016/S1470-2045(15)00465-9