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As researchers have learned more about the changes inside cells that cause cancer, they have developed newer drugs that target these changes. These are often referred to as targeted therapy drugs. These drugs work differently from standard chemotherapy (chemo) drugs. They sometimes work when chemo drugs don’t, and they often have different side effects.

Bruton tyrosine kinase (BTK) inhibitors

Ibrutinib (Imbruvica) and zanubrutinib (Brukinsa) block a protein called Bruton tyrosine kinase (BTK) inside lymphoma cells, which normally helps the cells grow and survive. Ibrutinib can be used alone or in combination with rituximab to treat WM, while zanubrutinib is typically used by itself. These drugs are taken by mouth as pills, typically once or twice a day.

Common side effects of BTK inhibitors include diarrhea, rash, muscle and bone pain, fatigue, cough, bruising, and low blood cell counts. More serious side effects can include bleeding, serious infections, and heart rhythm problems. Some people taking these drugs develop skin or other cancers, so it’s important to use sun protection when outside while taking one of these drugs.

Proteasome inhibitors

These drugs stop enzyme complexes (proteasomes) inside cells from breaking down proteins that normally help keep cell division under control.

Bortezomib (Velcade) and carfilzomib (Kyprolis) are sometimes helpful in treating WM. These drugs are given as an infusion into a vein (IV); bortezomib can also be given as an injection under the skin (sub-q).

Although these drugs work slightly differently from most chemo drugs, they can still cause many of the same types of side effects, including low blood counts, nausea, and loss of appetite. They can also damage nerves, causing pain in the feet and legs (peripheral neuropathy). The nerve damage usually gets better after the drug is stopped, but it might not go away completely.

mTOR inhibitors

These drugs 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 also been shown to be useful in treating WM after other treatments have been tried. This drug is taken daily as a pill. Common side effects include fatigue (tiredness), mouth pain, rash, diarrhea, and infections.

Other mTOR inhibitors, such as temsirolimus (Torisel), are now being studied to see if they can help treat WM as well.

Other drugs that target different parts of lymphoma cells are also being studied for use against WM (see What’s New in Waldenstrom Macroglobulinemia Research?).