Targeted Drugs for Waldenstrom Macroglobulinemia

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

Proteasome inhibitors

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

Bortezomib (Velcade^®) is often used to treat multiple myeloma and some types of lymphoma. It has also been found to be helpful in some cases of WM. This drug is given as an infusion into a vein (IV) or an injection under the skin (sub-q).

Other proteasome inhibitors, such as carfilzomib (Kyprolis^®), are now being studied to see if they can help treat WM as well.

Although these drugs work in a slightly different way 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. 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.

Bruton tyrosine kinase (BTK) inhibitors

Ibrutinib (Imbruvica^®) blocks a protein called Bruton tyrosine kinase (BTK) inside lymphoma cells, which normally helps the cells grow and survive. This drug can be used to treat some types of lymphoma, including WM. Ibrutinib is taken by mouth, once a day. Common side effects include diarrhea or constipation, nausea and vomiting, fatigue, swelling, decreased appetite, and low blood counts.

Other drugs that block BTK or other kinases in lymphoma cells are also being studied for use against WM (see What’s New in Waldenstrom Macroglobulinemia Research and Treatment?).