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ASH 2022: Dr. Richard Furman on Acalabrutinib for Treatment of Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

In science and medicine, information is constantly changing and may become out-of-date as new data emerge.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.

This article has been medically reviewed by Dr. Brian Koffman on April 24, 2023.

The Bottom Line:

The long-term follow-up results from a phase 1/2 clinical trial of acalabrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) further confirm that acalabrutinib is safe and effective.

Who Performed the Research and Where Was it Presented:

Dr. Richard Furman from Weill Cornell Medicine and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.

Background:

Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that is very effective for treating CLL / SLL. However, its use has been linked to an increased risk of developing cardiovascular side effects such as atrial fibrillation, ventricular arrhythmias, and hypertension. Acalabrutinib is a more specific next-generation BTK inhibitor with a better safety profile (fewer side effects) than ibrutinib.

In this video, Dr. Alexey Danilov, Associate Director of the Toni Stephenson Lymphoma Center at the City of Hope in Duarte, CA, interviewed Dr. Richard Furman, Director of the CLL Research Center at Weill Cornell Medicine in New York, NY. They discussed the final results of a phase 1/2 trial of acalabrutinib in patients with relapsed/refractory CLL / SLL.

Methods and Participants:

This was a phase 1/2 clinical trial of acalabrutinib in patients with relapsed/refractory CLL / SLL who had previously received one or more treatments. While different doses were used in different portions of the study, the final dosing regimen was 100 mg acalabrutinib twice per day.

Results:

  • A total of 134 patients were treated, and at the end of the study, the median follow-up time was 53 months (~4.5 years).
  • Common side effects included diarrhea (54%), headache (51%), fatigue (37%), joint pain (35%), and nausea (35%).
  • The rate of atrial fibrillation (abnormal heart rhythm) was 9%, lower than what is typically seen with ibrutinib (15%). 
  • No new safety signals emerged with longer follow-ups.
  • Ninety percent of patients responded to treatment, and the median duration of response was five years.
  • Now that both acalabrutinib and zanubrutinib are approved for treating CLL / SLL, it makes sense to use these agents. They are equally effective as ibrutinib but have less potential for cardiac side effects.
  • Additionally, a tablet formulation of acalabrutinib was approved last year, which makes it possible to use in patients who are also on proton-pump inhibitors (which reduce stomach acid) or who have difficulty swallowing capsules.
  • While acalabrutinib and zanubrutinib have not been directly compared, they appear equally effective and have slightly different side effect profiles.

Conclusions:

The findings further confirm the safety and efficacy of acalabrutinib for treating CLL / SLL. The results are similar to those seen in larger phase 3 clinical trials, which have compared acalabrutinib vs. chemoimmunotherapy (ASCEND) and acalabrutinib vs. ibrutinib (ELEVATE R/R).

Links and Resources:

Watch the interview on the abstract here:

ASH 2022: Richard Furman on Acalabrutinib for Treatment of CLL / SLL

You can read the actual ASH abstract here: Phase 1/2 Study of Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Final Results with >4 Years of Follow-up

Take care of yourself first.

Ann Liu, PhD