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ASH 2021: Dr. John Seymour on Side Effects of Acalabrutinib vs. Ibrutinib in Chronic Lymphocytic Leukemia (CLL)

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Ibrutinib is a Bruton tyrosine kinase (BTK) inhibitor that is very effective for treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL). However, it must be taken continuously for an indefinite duration until the disease progresses or the patient develops intolerance to the drug. In addition, Ibrutinib use has been linked to an increased risk of cardiovascular side effects such as abnormal heart rhythms and high blood pressure. Acalabrutinib is a next-generation BTK inhibitor that is thought to have a better safety profile (fewer side effects) than ibrutinib. Previous clinical trial results have shown that acalabrutinib is as effective as ibrutinib and is easier to tolerate. See our previous coverage here and here.

At the American Society of Hematology (ASH) 2021, our own Dr. Brian Koffman interviewed Dr. John Seymour, Director of the Department of Hematology at Peter McCallum Cancer Center in Melbourne, Australia. They discussed updated safety results from the ELEVATE R/R study, which is the first study comparing acalabrutinib with ibrutinib head-to-head in patients with relapsed/refractory CLL.


  • The ELEVATE R/R study is a phase 3 clinical trial comparing twice-daily acalabrutinib with once-daily ibrutinib in patients with relapsed/refractory CLL.
  • Patients have been on treatment for three years at this point in the study.
  • Progression-free survival is equivalent between the two groups, meaning that acalabrutinib and ibrutinib are equally effective for preventing disease progression.
  • Researchers wanted to look at tolerance, toxicity, and quality of life, so they measured how often side effects (adverse events) occurred, how long those side effects lasted, and also adjusted for the amount of time a patient had been on the drug.
  • Incidence of potentially serious side effects such as irregular heartbeat (atrial fibrillation) and high blood pressure (hypertension) was lower in the acalabrutinib group compared with the ibrutinib group.
  • All grade bleeding events were less common with acalabrutinib, while major bleeding events were not statistically different.
  • The incidence of bothersome but less serious side effects such as diarrhea, joint pain, back pain, bleeding, and muscle spasms was lower in the acalabrutinib group than in the ibrutinib group.
  • The only side effects that had a somewhat higher incidence in the acalabrutinib group were headache and cough.
  • Headaches are a known side effect when starting treatment with acalabrutinib, but they usually go away after 2 to 6 weeks.
  • Approximately 14% of patients in the acalabrutinib group discontinued due to an adverse event, and 23% of patients in the ibrutinib group discontinued due to an adverse event.


The results of this study have been eagerly anticipated for quite a while. While both ibrutinib and acalabrutinib are equally effective for controlling CLL and SLL, acalabrutinib is easier to tolerate with fewer side effects. This is excellent news for patients and gives patients and doctors another option in the CLL / SLL treatment toolbox.

Please enjoy this interview with Dr. Seymour from the ASH meeting, held in December 2021 in Atlanta, GA, and virtually.

You can read the actual abstract here: Characterization of Bruton Tyrosine Kinase Inhibitor (BTKi)-Related Adverse Events in a Head-to-Head Trial of Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia (CLL)

Take care of yourself first.

Ann Liu, PhD