Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that is very effective for treating chronic lymphocytic leukemia (CLL). However, it must be taken continuously for an indefinite duration, and its use has been linked to increased risk of developing cardiovascular side effects such as atrial fibrillation, ventricular arrhythmias, and hypertension. Acalabrutinib is a next-generation BTK inhibitor that is thought to have a better safety profile (fewer side effects) than ibrutinib, but the two have never been directly compared in clinical trials before.
At the annual meeting of the American Society of Clinical Oncology (ASCO) 2021, our own Dr. Brian Koffman interviewed Dr. Matthew Davids, Associate Director of the Center for Chronic Lymphocytic Leukemia (CLL) at Dana-Farber Cancer Institute in Boston, MA. They discussed new data from the ELEVATE R/R study, which is comparing acalabrutinib with ibrutinib head-to-head in high-risk patients with relapsed/refractory CLL and del(17p) or del(11q).
Takeaways:
- This is the first study directly comparing two BTK inhibitors (acalabrutinib vs. ibrutinib) in patients with CLL.
- Over 500 patients with CLL who had been previously treated and had del(17p) or del(11q) participated in this study.
- Progression free survival was identical with acalabrutinib or ibrutinib (38.4 months) meaning that they are equally effective.
- Fewer patients in the acalabrutinib group experienced atrial fibrillation (abnormal heart rhythm) compared with ibrutinib group.
- Fewer patients in the acalabrutinib group experienced high blood pressure compared with the ibrutinib group.
- More patients in the acalabrutinib group experienced headaches compared with ibrutinib group.
- There were no differences in rates of infections, major bleeding, or Richter syndrome between the two groups.
- This study confirms that acalabrutinib is just as effective as ibrutinib, and it is easier to tolerate especially for older patients who are at higher risk of developing complications.
- If you are a patient currently taking ibrutinib and tolerating it well, there’s no need to switch. However, if you do develop side effects from ibrutinib, talk to your doctor about whether switching to acalabrutinib makes sense for you.
Conclusions:
The results of this study have been eagerly anticipated for a long time and it confirms what researchers have suspected: acalabrutinib is just as effective as ibrutinib and it is safer because it produces fewer cardiovascular side effects. Comparative trials such as this are very important for informing clinical decisions about which drugs to use. As CLL researchers move into studying combination therapies, it makes sense to use the drugs with the best safety profiles (fewest side effects) moving forward.
Please enjoy this interview with Dr. Davids from June 2021 at the ASCO virtual conference.
You can read the actual abstract here: First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia
Take care of yourself first.
Ann Liu, PhD
