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ASH 2022: Time to Next Therapy with Acalabrutinib vs Ibrutinib

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Medically reviewed by Dr. Brian Koffman

The Bottom Line:

This real-world study found that patients with chronic lymphocytic leukemia (CLL) treated with first-line acalabrutinib were more likely to need to change therapies or add an additional therapy compared with patients treated with ibrutinib.

Who Performed the Research and Where Was it Presented:

Dr. Ryan Jacobs from Atrium Health Levine Cancer Institute and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2022.


Currently, three BTKi are approved for treating CLL: ibrutinib, acalabrutinib, and zanubrutinib. While acalabrutinib and zanubrutinib have been directly compared with ibrutinib in clinical trials in relapsed/refractory CLL, these BTKi have never been directly compared as first-line treatments. This is an important gap in knowledge because BTKi is often used as a first-line therapy. Real-world data can help fill this knowledge gap and provide important information about these treatments’ effectiveness in a more diverse real-world patient population.

Methods and Participants:

This study used electronic medical record data to identify adults with CLL who initiated ibrutinib or acalabrutinib as a first-line therapy on or after the date of acalabrutinib approval for CLL (11/21/2019). Patients were excluded if they had been treated with any other cancer treatments in the previous 12 months or started another cancer therapy within 28 days of beginning BTKi. Time to next therapy was defined as the time from the start of BTKi therapy to the initiation of the next or additional treatment. Time to next therapy can be considered a real-world marker of disease progression.


  • The analysis included data from 710 patients treated with ibrutinib and 373 patients treated with acalabrutinib between 2019 and 2022.
  • A higher proportion of patients in the ibrutinib cohort had chronic pulmonary disease, peripheral vascular disease, and hypertension.
  • The mean follow-up was 17 months for the ibrutinib cohort and 13 months for the acalabrutinib cohort.
  • More patients in the acalabrutinib cohort (4.3%) added an anti-CD20 antibody within six months of initiating therapy than the ibrutinib cohort (0.6%).
  • During the study period, more patients in the acalabrutinib cohort (7.5%) started a subsequent or additional treatment than the ibrutinib cohort (5.9%).
  • After adjusting for baseline characteristics, patients treated with acalabrutinib were 89% more likely to start a subsequent or additional treatment than those treated with ibrutinib.
  • At 15 months, 95% of patients in the ibrutinib cohort and 88% in the acalabrutinib cohort had not initiated the subsequent therapy. This indicates that for the vast majority of patients, their disease was well-controlled with BTKi.


This study found that patients on first-line acalabrutinib were slightly more likely to need to change therapies or add an additional therapy than patients on ibrutinib. We don’t know what is causing these differences. Further research is needed to determine if this finding is reproducible and to determine what might be causing the differences between acalabrutinib and ibrutinib.

Links and Resources:

Here is where you can read the actual ASH abstract: Real-World Comparison of Time to Next Treatment for Patients with CLL Initiated on First-Line Treatment with Ibrutinib Versus Acalabrutinib

Take care of yourself first.

Ann Liu, PhD