The Bottom Line:
While atrial fibrillation while taking ibrutinib is not uncommon among patients treated for chronic lymphocytic leukemia (CLL), an irregular beat of this minor heart chamber doesn’t usually result in death. However, the research by a unit of the National Institutes of Health (NIH) disclosed a small but significant number of sudden deaths over the past decade among NIH patients and offers advice about how patients who need ibrutinib should be thoroughly tested for the potential for cardiac issues before starting treatment.
Who Performed the Research and Where Was it Presented?
Dr. Clare Sun, an Associate Research Physician at the National Heart, Lung, and Blood Institute (NHLBI), a part of the NIH, is one of the eight co-authors of the report presented in December 2022 at the American Society of Hematology (ASH) annual conference.
Dr. Sun was interviewed by Dr. Brian Koffman, a physician, CLL patient, and executive vice president and chief medical officer of CLL Society, at the ASH 2022 meeting in New Orleans. In the interview, she elaborates on the research results and recommendations on how patients can avoid cardiac issues while taking ibrutinib or other Bruton’s tyrosine kinase (BTK) inhibitors.
Method and Participants:
Electronic medical records of 131 NIH patients with CLL who had died from 2012-2022 while using ibrutinib were reviewed for prior cardiac symptoms, testing, and autopsy results. Records of the subset of patients with reported sudden death were also analyzed for 41 genes associated with inherited and syndromic conditions involving cardiac arrhythmias and the level of ibrutinib in stored blood samples.
- In this study, the term “sudden death” describes someone passing suddenly without an apparent cause. Most sudden death is thought to be from cardiac causes.
- The NHLBI researchers found that 3.8% of its ibrutinib-using CLL patients had a sudden death.
- The NHLBI study found that the five sudden death cases among 131 patients were due to cardiac abnormalities, including issues involving the major chambers of the heart, the ventricles.
- All five sudden deaths occurred in patients who weighed more than their ideal body weight.
- Genetic testing did not indicate any congenital association relating to sudden cardiac death.
- The incidence of sudden death was 801 per 100,000 patient years. This was much higher than 102 per 100,000 patient-years in a similar age-matched population who were not on ibrutinib.
- The NHLBI has a study to determine if extensive cardiac testing of CLL patients needing a BTK inhibitor such as ibrutinib can reduce the incidence of arrhythmias.
Conclusions and Comments:
CLL patients should disclose any prior cardiac issues to their hematology oncologist, and any who may need a BTK inhibitor should be tested for potential cardiac irregularities before beginning treatment. While the incidence of heart issues such as atrial fibrillation is unusual for patients using a BTK inhibitor, the occurrence of sudden death was even rarer in this research report’s relatively small sample size.
This paper reminds us that while ibrutinib and other BTK inhibitors, as well as other novel agents, are amazing drugs, there are some risks. I have a friend with blood cancer who took ibrutinib as part of a clinical trial for several months until minor atrial fibrillation occurred. He was told to stop the medication last year. Fortunately, he remains in remission thanks to ibrutinib. And we’re hoping the fast-evolving drug development scene will eventually provide him with the benefits of the BTK inhibitor but with fewer and lower risks.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Ibrutinib-Associated Sudden Death in Patients with CLL
CLL Society has this basic background article describing how ibrutinib can cause atrial fibrillation.
Larry Marion was diagnosed with CLL in 2005. During the past 17 years, he had 11 cycles of chemo, 5.5 years of ibrutinib, and 1.25 years of venetoclax to achieve an undetectable level of the disease in late 2020. He was a writer and editor for various business technology publications before he retired in 2019. For more information about his journey, click this link.