CLL Monthly MinutesLeukemia

Acalabrutinib versus Ibrutinib in Previously Treated CLL

The first head-to-head trial of these drugs shows comparable efficacy with a better cardiovascular safety profile for acalabrutinib.
Web Exclusives – September 20, 2021

For many patients with chronic lymphocytic leukemia (CLL), drugs called Bruton tyrosine kinase (BTK) inhibitors have become a mainstay of treatment since ibrutinib was first introduced in 2013.1 Despite advancing treatment for CLL, ibrutinib has been associated with potentially serious side effects, particularly those affecting the heart and cardiovascular system.1,2 A next-generation BTK inhibitor, acalabrutinib, has been developed to maximize the efficacy of this class of drugs, while limiting the side effects that were seen with ibrutinib.1

Recently, investigators reported the first results of the ELEVATE-RR clinical trial (NCT02477696;, which compared ibrutinib versus acalabrutinib in previously treated patients with high-risk CLL.3,4 All patients in this trial had received ≥1 prior treatments for their CLL and had cancers with certain genetic mutations, called del(17p) or del(11q), which are expected to lead to a poorer clinical outcome.3-5

The ELEVATE-RR study was designed to compare how long patients survived without disease progression on each of the 2 treatments.3,4 Other outcomes that were assessed were the number of patients developing an abnormal heart rhythm (atrial fibrillation), having a serious infection, undergoing transformation from CLL to a more severe type of lymphoma (also called a Richter transformation), and the total amount of time that patients survived after beginning treatment.3,4

A total of 533 patients were included in the study, with 268 receiving acalabrutinib and 265 receiving ibrutinib.3 As is typical for patients with CLL, half of the study participants were aged >66 years.3 Most patients had received ≥2 prior therapies before enrolling in the study.3

Looking at efficacy, the investigators found no difference between acalabrutinib and ibrutinib. The median survival time without disease progression was 38.4 months for both groups.3 With regard to safety, patients receiving acalabrutinib had a lower likelihood of developing an abnormal heart rhythm than those receiving ibrutinib.3 No differences were seen between the 2 drugs with regard to the frequencies of developing a serious infection or having a Richter transformation to lymphoma.3 At the time the data were presented, investigators could not conclude whether there was any difference in overall survival between the 2 treatments.3

High blood pressure, joint pain, diarrhea, headache, and cough were side effects that affected >20% of patients in either treatment group.3 Of these, only headache and cough were more commonly seen in patients receiving acalabrutinib than in those receiving ibrutinib.3 Among other side effects that were infrequent, but of clinical interest, bleeding events and events affecting the heart were less frequent with acalabrutinib than with ibrutinib.3 Together, side effects caused fewer patients receiving acalabrutinib to quit the study compared with ibrutinib.3

Overall, the results of ELEVATE-RR indicate that for previously treated patients with high-risk CLL, acalabrutinib is just as effective as ibrutinib with fewer cardiovascular complications.3


  1. Isaac K, Mato AR. Acalabrutinib and its therapeutic potential in the treatment of chronic lymphocytic leukemia: a short review on emerging data. Cancer Manag Res. 2020;12:2079-2085.
  2. Salem JE, Manouchehri A, Bretagne M, et al. Cardiovascular toxicities associated with ibrutinib. J Am Coll Cardiol. 2019;74:1667-1678.
  3. Hillmen P, Byrd JC, Ghia P, et al. First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia. Presented at the 2021 European Hematology Association Meeting, June 9, 2021. Abstract S145.
  4. Study of acalabrutinib (ACP-196) versus ibrutinib in previously treated subjects with high-risk CLL. Accessed August 23, 2021.
  5. Hewamana S, Dearden C. Treatment options for high-risk chronic lymphocytic leukaemia. Ther Adv Hematol. 2011;2:147-159.

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Last modified: September 20, 2021

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