Statin use during targeted therapy treatment led to a 61% improvement in the risk of dying of cancer for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to the results of a study published in Blood Advances. The investigators sought to determine the effect of status use on survival outcomes in patients with CLL/SLL receiving contemporary treatment regimens, including those with ibrutinib and other Bruton’s tyrosine kinase inhibitors.
“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,” stated principal investigator Ahmad Abuhelwa, PhD, Assistant Professor of Pharmacy Practice and Pharmacotherapeutics at the University of Sharjah in the United Arab Emirates. “Our results highlight a strong link between statin use and improved survival in this patient population.”
Study Methods and Results
A total of 1,467 patients with CLL/SLL were assessed from four randomized trials that were conducted between 2012 and 2019: RESONATE, RESONATE-2, iLLUMINATE, and HELIOS. The experimental arm in each trial included ibrutinib either as a single agent or in a combination regimen. A total of 29% of all participants were taking a statin at the time of treatment initiation across all these studies.
The use of statins was associated with an improvement in both overall survival (adjusted hazard ratio [HR] = 0.55; 95% confidence interval [CI] = 0.42–0.72; P < .001) and progression-free survival (adjusted HR = 0.73; 95% CI = 0.61–0.88; P = .001). Cancer-specific survival showed the most significant impact (adjusted HR = 0.39; 95% CI = 0.22–0.70; P = .001).
The findings were consistent regardless of treatment arm, with or without ibrutinib (overall survival P interaction = 0.52; progression-free survival P interaction = 0.31) and diagnosis of CLL or SLL (overall survival P interaction = 0.77; progression-free survival P interaction = 0.32).
“These findings don’t allow us to say for certain that statins directly improve cancer outcomes,” Dr. Abuhelwa said. “However, the fact that this association remained strong even after accounting for multiple factors makes it an important area for future research.” As next steps, he recommended conducting laboratory studies to better understand how statins may influence cancer biology, as well as prospective clinical trials in which patients with CLL or SLL are randomly assigned to take a statin or not.
Further, statin use did not show a significant association with grade 3 or higher adverse events.
The study was not able, however, to determine the effects of specific statin types, doses, or duration on patient survival, meaning the results cannot be directly applied to treatment yet. “While our results are very promising, we can’t recommend starting statins for CLL/SLL treatment based on this study alone,” Dr. Abuhelwa concluded. “Future clinical trials are needed to determine definitively whether statins have a direct benefit on cancer survival.”
Disclosure: For full disclosures of the study authors, visit ashpublications.org/bloodadvances.
