What Are BTK Inhibitors for Lymphoma?

One type of treatment for lymphoma is a targeted therapy called BTK inhibitors. Learn how these treatments work, the different types of BTK inhibitors, typical side effects, and ways lymphoma specialists are working to improve the effectiveness of BTK inhibitors in the future. 

What are BTK inhibitors? 

BTK inhibitors are a type of cancer treatment called a targeted therapy. Targeted therapy uses medication to stop cancer cells from growing. It does this by targeting specific proteins or molecules in cancer cells. BTK inhibitors target the Bruton’s tyrosine kinase (BTK) protein found in B cells. 

B cells are a type of white blood cell that helps the body fight infection. The BTK protein helps healthy B cells grow. B-cell lymphomas have dysfunctional B cells with an overactive BTK protein. This helps the cancer cells grow out of control and survive longer than a normal B cell. 

BTK inhibitors block the activation of the BTK protein and stop the growth of lymphoma cells. 

How are BTK inhibitors given?

BTK inhibitors are currently administered as a continuous-duration therapy for lymphoma. This means the medicine is taken indefinitely until the side effects outweigh the benefits of treatment or the lymphoma cells become resistant to BTK inhibitors.  

What are the FDA-approved BTK inhibitors for lymphoma?

BTK inhibitor for follicular lymphoma

• Zanubrutinib (Brukinsa, BeOne Medicines)

BTK inhibitors for mantle cell lymphoma (MCL)

• Ibrutinib (Imbruvica, Pharmacyclics/Johnson & Johnson)
• Acalabrutinib (Calquence, AstraZeneca)
• Zanubrutinib
• Pirtobrutinib (Jaypirca, Eli Lilly)

BTK inhibitor for marginal zone lymphoma (MZL)

• Ibrutinib

BTK inhibitors for small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) 

• Ibrutinib
• Acalabrutinib
• Zanubrutinib
• Pirtobrutinib

BTK inhibitor for Waldenström’s macroglobulinemia (WM)

• Ibrutinib 

What are the differences between first-generation and next-generation BTK inhibitors? 

The first FDA-approved BTK inhibitor was ibrutinib, so it is considered a first-generation BTK inhibitor. Although it helps limit lymphoma progression for many patients, it has a higher risk of atrial fibrillation, a condition that causes an abnormal heartbeat. Atrial fibrillation may lead to stroke if not managed. 

Later, next-generation BTK inhibitors acalabrutinib, zanubrutinib, and pirtobrutinib were FDA-approved. These newer lymphoma treatment options improve effectiveness over ibrutinib and have fewer heart-related side effects. 

What are the differences between covalent and non-covalent BTK inhibitors? 

Another distinction between BTK inhibitors is that there are covalent and non-covalent versions. 

Covalent BTK inhibitors, such as acalabrutinib, zanubrutinib, and ibrutinib, permanently bind to the BTK protein. After several years of exposure, the lymphoma cell often finds a way to mutate its BTK proteins, causing BTK inhibitors to stop working. When this happens, patients are considered to be covalent BTK inhibitor-resistant and, therefore, not eligible to continue treatment with these agents. 

The non-covalent BTK inhibitor pirtobrutinib binds to the BTK protein non-permanently through hydrogen and ionic bonds. This altered way of binding helps stop the activation of the BTK protein despite BTK mutations from prior use of covalent BTK inhibitors. Click here to learn more about pirtobrutinib. 

What are the side effects of BTK inhibitors? 

Common side effects of BTK inhibitors include infections, fatigue, easy bruising or bleeding, muscle pain, and headache. Talk to your lymphoma specialist about ways to manage BTK inhibitor side effects. In addition, you can click here to review resources.

Clinical trials for BTK inhibitors 

To improve the effectiveness of BTK inhibitors, several clinical trials are ongoing to evaluate different treatment strategies. Some of these include: 

• Combining BTK inhibitors with other lymphoma treatments
• Evaluating new non-covalent BTK inhibitors
• Moving pirtobrutinib to be a first-line treatment rather than for only relapsed/refractory lymphoma 

To review available clinical trials and expand your access to innovative treatments, click the button below! 

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Summary 

BTK inhibitors are a targeted treatment for certain types of B-cell lymphomas. They target the overactive BTK protein in lymphoma cells to disrupt their growth. BTK inhibitors include first-generation ibrutinib and next-generation acalabrutinib, zanubrutinib, and pirtobrutinib. They differ in how they bind to lymphoma cells and side effects, with the newer BTK inhibitors offering fewer heart-related complications than ibrutinib. Ongoing clinical trials aim to enhance the effectiveness of these treatments for people with lymphoma. 

Continue Reading Lymphoma News

Sources:

• Imbruvica Prescribing Information
• Brukinsa Prescribing Information
• Calquence Prescribing Information
• Jaypirca Prescribing Information
• Nemtabrutinib (MK-1026)
• Zanubrutinib + Sonrotoclax
• ALPINE Study Updates: Zanubrutinib vs Ibrutinib
• MAJIC Study Acalabrutinib + Venetoclax
• Acalabrutinib vs Ibrutinib