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ASH 2022: Dr. John Seymour on the Adverse Event Burden of Acalabrutinib vs. Ibrutinib in Patients with 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In science and medicine, information is constantly changing and may become out-of-date as new data emerge.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.

The Bottom Line:

This new data analysis from a clinical trial directly comparing acalabrutinib vs. ibrutinib used a novel methodology incorporating adverse event (side effect) duration and severity to calculate adverse event burden. It further confirms that acalabrutinib is better tolerated compared with ibrutinib.

Who Performed the Research and Where Was it Presented:

Dr. John Seymour from Peter MacCallum Cancer Centre and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.


Bruton tyrosine kinase (BTK) inhibitors have revolutionized the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Acalabrutinib is a next-generation BTK inhibitor that is thought to have a better safety profile (fewer side effects) than ibrutinib, which has known cardiovascular side effects. Still, the two had never been directly compared in clinical trials before.

In this interview, our own Dr. Brian Koffman interviewed Dr. John Seymour, Director of the Department of Hematology at Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Melbourne, Australia. They discussed the latest updates to the safety data from the ELEVATE R/R study, which was the first clinical trial to compare acalabrutinib and ibrutinib head-to-head.

Methods and Participants:

The ELEVATE R/R study is a phase 3 clinical trial directly comparing acalabrutinib with ibrutinib in high-risk patients with relapsed/refractory CLL and del(17p) or del(11q). Over 500 patients participated in this study. Patients received either acalabrutinib 100 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity.


  • Previously published results from the ELEVATE R/R study showed that acalabrutinib was equally effective as ibrutinib for treating relapsed/refractory CLL.
  • Acalabrutinib also had an improved safety profile with statistically fewer atrial fibrillation/flutter (abnormal heart rhythm) events (9% vs. 16%) and numerically fewer discontinuations due to adverse events (15% vs. 21%) vs. ibrutinib.
  • More details on these results can be found in our previous coverage here and here, as well as in this paper.
  • This new study data analysis used a novel method to calculate an adverse event burden score.
  • Traditionally, clinical trials have evaluated safety by collecting data on the number of times an adverse event occurs during the trial (incidence). However, this doesn’t tell us much about how bothersome the adverse events were, which could be especially important for drugs that need to be taken indefinitely, such as BTK inhibitors.
  • This new method for calculating the adverse event burden score takes into account the severity of the adverse event and the duration of the adverse event in addition to the normal incidence data.
  • Higher adverse event burden scores indicate increased severity and longer duration of the side effect.
  • The adverse event burden scores for atrial fibrillation (abnormal heart rhythm), hypertension (high blood pressure), hemorrhage, and musculoskeletal events (joint pain, muscle pain, muscle spasms) were significantly higher with ibrutinib.
  • The adverse event burden scores for headaches and diarrhea were significantly higher with acalabrutinib.


This new analysis using methodology incorporating adverse event duration and severity confirms that acalabrutinib is better tolerated than ibrutinib. It also confirms the safety differences that have been reported previously between the two drugs.

Links and Resources:

Watch the interview on the abstract here:

You can read the actual ASH abstract here: Assessing the Burden of 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