BTK Inhibitors as Frontline Therapy for CLL

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William Wierda, MD, PhD: Hello, and welcome to this OncLive® Peer Exchange entitled, “Recent Advances in the Treatment of Chronic Lymphocytic Leukemia.”

I’m Dr William Wierda, professor of medicine in the Department of Leukemia and section head for chronic lymphocytic leukemia [CLL] at The University of Texas MD Anderson Cancer Center in Houston, Texas.

I’m joined today by a panel of experts in CLL and I would like to welcome them and invite each of them to introduce themselves. We’ll start with Jackie Barrientos.

Jacqueline Barrientos, MD, MS: Hi, my name is Jacqueline Barrientos, and I am professor of medicine at the Zucker School of Medicine at Hofstra/Northwell [New Hyde Park, New York]. I do work at the CLL Research and Treatment Program in Long Island, New York.

Catherine Callaghan Coombs, MD: Hi there, I’m Callie Coombs. I’m at the University of North Carolina [Chapel Hill, North Carolina], where I work as an assistant professor of medicine within the Department of Hematology mostly caring for patients with CLL.

Nicole Lamanna, MD: Hi, my name is Nicole Lamanna. I’m at Columbia Universality Medical Center [New York, New York] on the Leukemia Service and director of the CLL Program here.

Anthony Mato, MD, MSCE: Hi everybody, Anthony Mato from Memorial Sloan Kettering Cancer Center [New York, New York], director of the CLL Program and very happy to be here today.

Deborah M. Stephens, DO: Hi, I’m Debbie Stephens. I’m at the Huntsman Cancer Institute at the University of Utah [Salt Lake City, Utah], and I direct the CLL Program here.

William Wierda, MD, PhD: Great. Welcome everybody and thank you for joining me today. We’re going to discuss a number of recent updates in the treatment of CLL that were presented at conferences over 2021, particularly focusing on the ASH [American Society of Hematology meeting] 2021 updates. We’ll discuss the data in the context of standards of care and guidelines for treatment and how these updates impact on our management of our patients with CLL.

We’ll start with targeted therapy, which began with [the] Bruton tyrosine kinase [BTK] inhibitor, ibrutinib [Imbruvica®], which has been available for several years now. We’ve learned over the years that CLL cells are dependent on the kinase activity of Bruton tyrosine kinase for survival, and ibrutinib was the first small molecule inhibitor that was developed, first in the laboratory and then clinically in treatment of patients with CLL. This is an irreversible inhibitor, meaning that it binds covalently to BTK at the cysteine 481 moiety and in doing so it blocks the ATP [adenosine-triphosphate]-binding pocket and inactivates BTK irreversibly. And the only way to replace functional BTK would be resynthesis.

Transcript edited for clarity.