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ASH 2021: Dr. Jeff Sharman on Zanubrutinib for BTK Inhibitor-Intolerant 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In science and medicine, information is constantly changing and may become out-of-date as new data emerge.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.

Chemotherapy was the only treatment available to CLL / SLL patients until the BTK inhibitor ibrutinib was developed and revolutionized the treatment of CLL / SLL.

Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib are very effective for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Still, they must be taken continuously, and some patients can have trouble tolerating their side effects. Therefore, second-generation BTK inhibitors such as acalabrutinib and zanubrutinib have been designed with the goal of reducing side effects.

At the American Society of Hematology (ASH) 2021, our own Dr. Brian Koffman interviewed Dr. Jeff Sharman, a hematologist/oncologist at Willamette Valley Cancer Institute in Eugene, OR. They discussed zanubrutinib and its use in patients who could not tolerate previous BTK inhibitors.


  • BTK inhibitors are wonderfully effective, but the problem is that they do have side effects.
  • Even small to moderate side effects can be discouraging for patients when you have to take a drug indefinitely.
  • Some side effects patients may experience with ibrutinib include joint pain, muscle cramps, bruising, high blood pressure, and an irregular heartbeat (atrial fibrillation).
  • Second-generation BTK inhibitors such as acalabrutinib and zanubrutinib were designed to be more specific and minimize side effects.
  • In head-to-head studies, patients taking acalabrutinib or zanubrutinib have lower rates of high blood pressure and atrial fibrillation than those taking ibrutinib. See our previous coverage of these trials here and here.
  • For this phase 2 study, 64 patients who could not tolerate ibrutinib or acalabrutinib due to side effects were switched to zanubrutinib.
  • When patients switched to zanubrutinib, the symptom which previously caused them to stop taking their last BTK inhibitor did not recur in 73% of patients. If a symptom did recur, it tended to recur at a lower intensity.
  • When patients switched to zanubrutinib, they experienced fewer side effects or were better able to tolerate those side effects.
  • Additionally, patients demonstrated they maintained (41%) and improved (53%) responses with zanubrutinib treatment.


Zanubrutinib is not yet approved for CLL, but we are hopeful that an FDA approval will be coming in the near future (see our previous announcement here). Second-generation BTK inhibitors appear to be just as effective as ibrutinib but with fewer side effects making them less burdensome for patients.

Please enjoy this interview with Dr. Sharman from the ASH meeting, held in December 2021 in Atlanta, GA, and virtually.

You can read the actual abstract here: Phase 2 Study of Zanubrutinib in BTK Inhibitor-Intolerant Patients (Pts) with Relapsed/Refractory B-Cell Malignancies

Take care of yourself first.

Ann Liu, PhD