Targeted Therapy for Non-Hodgkin Lymphoma

Some newer drugs target the changes in lymphoma cells that help those cells grow. This is called targeted therapy. It is sometimes used as part of treatment for non-Hodgkin lymphoma (NHL).

Targeted therapy works differently from standard chemotherapy (chemo). Sometimes, targeted therapy drugs work when standard chemo drugs do not. They often have different types of side effects as well.

Proteasome inhibitors

Proteasome inhibitors are a type of targeted therapy that causes protein waste to build up in cancer cells.

Enzyme complexes inside cancer cells, known as proteasomes, have the job of breaking down proteins when they are no longer needed. Proteasome inhibitors stop this breakdown from happening, causing protein waste to build up inside the cancer cells. The cancer cells can no longer grow and divide, so they die.

Proteasome inhibitors are more often used to treat multiple myeloma, but they can also help treat some types of non-Hodgkin lymphoma (NHL).

Possible side effects of proteasome inhibitors

Side effects can be like those from standard chemo drugs, including:

• Low blood counts 
• Nausea 
• Loss of appetite
• Nerve damage

Histone deacetylase (HDAC) inhibitors

HDAC inhibitors work by blocking proteins called histones. These proteins help control which genes are turned on or off inside cancer cells. By blocking them, HDAC inhibitors can slow or stop the growth of lymphoma cells.

Three HDAC inhibitors are used to treat certain types of T-cell lymphoma, usually after at least one other treatment has been tried:

Possible side effects of HDAC inhibitors

Common side effects include:

• Nausea 
• Vomiting 
• Tiredness 
• Low red blood cell counts (anemia) 

Low platelet and white blood cell counts can also happen. This can increase the risk of bleeding and infection.

BTK inhibitors

Bruton tyrosine kinase (BTK) is a protein that normally helps some lymphoma cells (B cells) grow and survive. Drugs that target this protein are known as BTK inhibitors. They can be helpful in treating some types of B-cell non-Hodgkin lymphomas.

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

Possible side effects of BTK inhibitors

Common side effects of BTK inhibitors can include:

• Headache 
• Diarrhea
• Bruising
• Feeling tired
• Muscle and joint pain 
• Cough
• Rash
• Low blood cell counts

Less common but more serious side effects can include bleeding (hemorrhage), infections, and heart rhythm problems such as atrial fibrillation.

These drugs may also increase the risk of skin cancer or other cancers. If you are taking any of these drugs, it’s important to protect yourself from the sun when you are outside.

PI3K inhibitors

Phosphatidylinositol 3-kinases (PI3Ks) are a family of proteins that send signals in cells that can affect cell growth. Drugs that target these proteins are known as PI3K inhibitors. They can be helpful in treating some types of non-Hodgkin lymphoma.

Duvelisib (Copiktra) is the PI3K inhibitor currently approved to treat some non-Hodgkin lymphomas. Several other PI3K inhibitors were previously approved for NHL, but these have since been withdrawn from the US market due to safety concerns, including serious infections and secondary cancers.

Possible side effects of PI3K inhibitors

Common side effects include:

• Diarrhea 
• Fever 
• Fatigue 
• Nausea 
• Cough 
• Pneumonia 
• Belly pain 
• Joint and muscle pain 
• Rash

Low blood counts are also common, including low red blood cell counts (anemia) and low levels of certain white blood cells (neutropenia).

More serious side effects can occur, but these happen less often. They can include liver damage, severe diarrhea, lung inflammation (pneumonitis), serious allergic reactions, and severe skin problems.