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Which BTK Inhibitor is Best Upfront for CLL?

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March 4, 2021

The decision comes down to tolerability

  • Two BTK inhibitors — ibrutinib and acalabrutinib (brand name: Calquence) — are available for CLL
  • Ibrutinib has a longer track record, but comes with more potential side effects
  • For older patients with comorbidities, starting with acalabrutinib (brand name: Calquence) might be the better choice
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Ibrutinib was once the only bruton tyrosine kinase (BTK) inhibitor. Now that acalabrutinib (brand name: Calquence) is available, you have a decision to make when choosing an upfront therapy for your chronic lymphocytic leukemia (CLL) patients. Which of these two drugs is best?

Having two drugs available is a paradigm shift similar to what the chronic myeloid leukemia (CML) world went through a few years ago, Dr. Sikander Ailawadhi, hematologist-oncologist and professor of medicine at Mayo Clinic in Jacksonville, FL, tells SurvivorNet Connect. “Does it mean that the new shiny thing is always going to be better and you use it for everybody? I think the discussion is a little bit more nuanced than that,” he says.

On the one hand, ibrutinib has a much longer track record. The relative wealth of data to support its use makes it easier to determine, for example, how a patient might do on venetoclax once they progress from ibrutinib. Until more data are available, “it is important to keep in mind that there are patients who will tolerate ibrutinib and no reason to just switch to acalabrutinib necessarily, or across the board,” Dr. Ailawadhi says.

One justification for choosing acalabrutinib first is the potential for side effects with ibrutinib. For this reason, Dr. Ailawadhi often suggests that his older patients start on acalabrutinib to ensure they’ll adhere to their medication regimen. “When patients have quite a bit of comorbidities and there are concerns about pre-existing cardiac issues, it is a bit easier to start on acalabrutinib,” he says. “Bottom line is we want the patient to start on it, and stay on it.”