Continuous Therapy Options For CLL: Acalabrutinib vs. Zanubrutinib

As you continue to provide optimal treatment for your chronic lymphocytic leukemia (CLL) patients, you’ll likely be faced with the need for continuous therapy. The bruton tyrosine kinase (BTK) inhibitors acalabrutinib (Calquence) and zanubrutinib (Brukinsa) are next-generation treatments that have shown promise for progression-free survival during clinical trials.

Although the two BTK inhibitor drugs are similar in binding to the BTK proteins, preventing them from supporting cancer cell growth, choosing which one to prescribe could depend on patient preference and side effect profiles.

Dr. Adam Kittai, Associate Professor of Medicine (Hematology and Medical Oncology) at Mount Sinai in New York, tells SurvivorNet Connect his approach to choosing between the two rests on what his patient prefers.

“Do they want a time-limited therapy, or do they want a continuous therapy? And really patient preference is what I use to determine what to treat that patient with,” Dr. Kittai explains.

“Acalabrutinib versus zanubrutinib. It’s really up in the air. In my opinion. These two drugs are very similar. The only thing that we note that is different between these two drugs is that in the second line, Zanubrutinib did show an efficacy benefit compared to ibrutinib for all comers, whereas when acalabrutinib was compared to ibrutinib, no efficacy benefit was shown,” he adds.

“But this was in a high-risk group of patients with deletion 17 P and deletion 11 Q. So now when I’m thinking in the frontline, really there’s not much to differentiate between the two drugs, but mostly I go by their side effect profile.”

The Side Effect Profile

The FDA approved Zanubrutinib based on the results of two phase III clinical trials, the ALPINE and SEQUOIA.

The most common side effects for Zanubrutinib include:

• Common cold-like symptoms
• Constipation
• Diarrhea
• Nausea and Vomiting
• Tiredness
• Pains in bones, joints, muscles, neck, or back
• Spasms in muscles
• Headaches

Although very unlikely, some people may experience severe and/or life-threatening side effects, which include but are not limited to:

• Significantly elevated blood pressure that leads to headaches, dizziness, and changes in vision
• Blood in bowel movements
• Bleeding from the gums
• Easy bruising and bleeding after minor traumas
• Chest pain or pressure
• Shortness of breath
• Serious infections
• Reactivation of hepatitis B in patients who carry the virus
• Allergic reaction with symptoms such as rash, hives, swelling, itchiness, wheezing, and trouble breathing.
• Development of new cancers
• Harm to unborn babies

Known side effects of Acalabrutinib include:

• Headache
• Nausea
• Vomiting
• Constipation
• Diarrhea
• Abdominal pain
• Rash
• Light bruising or small red or purple spots on the skin
• Joint or muscle pain
• Extreme tiredness

Dr. Kittai says that while assessing his patient profiles, he notes their aversion to certain symptoms, like headaches, which is a potential side effect of the BTK inhibitors.

“Typically, I might avoid acalabrutinib in somebody who has chronic headaches, which I don’t want that to exacerbate, and Zanubrutinib seems to have more hypertension,” Dr. Kittai said.

Dr. Kittai advised doctors in the CLL community to familiarize themselves with Acalabrutinib and Zanubrutinib.

“Once you get familiar with one drug, you know how to dose, reduce it, dose hold it, know what side effects to tell your patients about,” Dr. Kittai said.