Targeted Therapy Drugs for Waldenstrom Macroglobulinemia

In recent years, new drugs that target specific parts of cancer cells have been developed. These targeted drugs work differently from standard chemotherapy drugs, and they can have different side effects than chemo. They can be used instead of chemo or along with it, in some situations.

Some targeted drugs can be useful in treating Waldenstrom macroglobulinemia.

Bruton tyrosine kinase (BTK) inhibitors

BTK inhibitors are drugs that block a protein inside lymphoma cells called Bruton tyrosine kinase. This protein normally helps the lymphoma cells grow and survive.

 Examples of BTK inhibitors include:

• Acalabrutinib (Calquence)
• Ibrutinib (Imbruvica) alone or in combination with immunotherapy
• Orelabrutinib
• Pirtobrutinib (Jaypirica)
• Tirabrutinib
• Zanubrutinib (Brukinsa)

These drugs are taken by mouth as pills, typically once or twice a day.

Possible side effects

Common side effects of BTK inhibitors include:

• Diarrhea
• Rash
• Muscle and bone pain
• Fatigue
• Cough
• Bruising
• Low blood cell counts

Less common but more serious side effects can include:

• Bleeding
• Serious infections
• Heart rhythm problems
• Skin cancer

Proteasome inhibitors

Proteasome inhibitors stop enzyme complexes (proteasomes) inside cells from breaking down proteins inside the cancer cells that are no longer needed. When this protein waste builds up, the cancer cells can’t grow and divide, causing them to die.

Examples of proteasome inhibitors include:

• Bortezomib (Velcade)
• Ixazomib (Ninlaro), sometimes in combination with immunotherapy and steroids
• Carfilzomib (Kyprolis)

These drugs can be given by mouth (ixazomib), injected under the skin (bortezomib), or as an infusion into a vein (bortezomib and carfilzomib).

Possible side effects

Common side effects of proteasome inhibitors are:

• Low blood counts
• Nausea
• Loss of appetite

They can also damage nerves, causing pain in the feet and legs called peripheral neuropathy. This nerve damage usually gets better after the drug is stopped, but it might not go away completely.

mTOR inhibitors

mTOR inhibitors block a cell protein known as mTOR, which normally helps cells grow and divide into new cells.

Everolimus (Afinitor) is used more often to treat some other types of cancer, but it has been shown to be useful in treating Waldenstrom macroglobulinemia after other treatments have been tried.

This drug is taken daily as a pill.

Possible side effects

Common side effects include:

• Fatigue (tiredness)
• Mouth pain
• Rash
• Diarrhea
• Infections

BCL-2 inhibitors

These drugs attack BCL-2, a protein that can help leukemia cells live longer.

Venetoclax (Venclexta) is one example. It may be used to treat Waldenstrom macroglobulinemia after other drugs have been tried.

These drugs are given by mouth as a tablet, usually once daily.

Possible side effects

The most common side effects of BCL-2 inhibitors are:

• Fever
• Feeling tired or weak
• Low appetite
• Nausea
• Diarrhea
• Low blood counts
• Swelling
• Skin rash
• Changes to some blood tests, which may need to be watched while getting the drug