Targeted Drug Therapy for Non-Hodgkin Lymphoma

As researchers have learned more about the changes in lymphoma cells that help them grow, they have developed newer drugs to specifically target these changes. These targeted drugs work differently from standard chemotherapy (chemo) drugs. Sometimes they work when standard chemo drugs don’t, and they often have different types of side effects. 

Proteasome inhibitors

These drugs work by stopping enzyme complexes (proteasomes) in cells from breaking down proteins important for keeping cell division under control. They are more often used to treat multiple myeloma, but they can be helpful in treating some types of non-Hodgkin lymphoma (NHL) as well.

Bortezomib (Velcade) is a proteasome inhibitor used to treat some lymphomas, usually after other treatments have been tried. Bortezomib is given as an infusion into a vein (IV) or an injection under the skin (subcutaneous, or sub-q), typically twice a week for 2 weeks, followed by a rest period.

Side effects can be similar to those of standard chemo drugs, including low blood counts, nausea, loss of appetite, and nerve damage.

Histone deacetylase (HDAC) inhibitor

HDAC inhibitors are drugs that can affect what genes are active by interacting with proteins in chromosomes called histones. 

Belinostat (Beleodaq) can be used to treat peripheral T-cell lymphomas, usually after at least one other treatment has been tried. It is given as an IV infusion, usually daily for 5 days in a row, repeated every 3 weeks.

Common side effects include nausea, vomiting, tiredness, and low red blood cell counts (anemia).

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, known as BTK inhibitors, 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.

Ibrutinib (Imbruvica) can be used to treat some types of NHL, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Acalabrutinib (Calquence) can be used to treat mantle cell lymphoma (typically after at least one other treatment has been tried), as well as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Zanubrutinib (Brukinsa) can be used to treat mantle cell lymphoma or marginal zone lymphoma, typically after at least one other treatment has been tried, as well as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Pirtobrutinib (Jaypirca) can be used to treat mantle cell lymphoma, typically after at least 2 other treatments (including another BTK inhibitor) have been tried.

Common side effects of BTK inhibitors can include headache, diarrhea, bruising, feeling tired, muscle and joint pain, cough, rash, and 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 or other cancers, so it’s important to use sun protection when outside while taking one of these drugs.

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, known as PI3K inhibitors, can be helpful in treating some types of non-Hodgkin lymphoma.

Copanlisib (Aliqopa) mainly targets the PI3K-alpha and PI3K-delta proteins. This drug can be used to treat follicular lymphoma, typically after other treatments have been tried. It’s given as an infusion into a vein, typically once a week for 3 weeks, followed by a week off.

Common side effects include high blood sugar levels, nausea, diarrhea, feeling weak, high blood pressure, low levels of white blood cells (with increased risk of infection), and low levels of blood platelets (with increased risk of bruising or bleeding). Less common side effects include infections, inflammation in the lungs, and severe skin reactions.

Duvelisib (Copiktra) blocks the PI3K-delta and PI3K-gamma proteins. This drug can be used to treat small lymphocytic lymphoma, typically after other treatments have been tried. It's a pill taken twice a day.

Common side effects include diarrhea, fever, fatigue, nausea, cough, pneumonia, belly pain, joint/muscle pain and rash. Low blood counts, including low red blood cell counts (anemia) and low levels of certain white blood cells (neutropenia) are also common. Less often, more serious side effects can occur, such as liver damage, severe diarrhea, lung inflammation (pneumonitis), serious allergic reactions, and severe skin problems.

EZH2 inhibitor

Tazemetostat (Tazverik) works by targeting EZH2, a protein known as a methyltransferase that normally helps some cancer cells grow. This drug can be used to treat follicular lymphomas with an EZH2 gene mutation, after other treatments have been tried. Tazemetostat can also be used to treat follicular lymphomas without an EZH2 mutation, if there are no other good treatment options available. This drug is taken as pills, typically twice a day.

The most common side effects of this drug include bone and muscle pain, feeling tired, nausea, belly pain, and cold-like symptoms. Tazemetostat can also increase the risk of developing some types of blood cancers.

Nuclear export inhibitor

The nucleus of a cell holds most of the cell’s important substances needed to make the proteins the cell uses to function and stay alive. A protein called XPO1 helps carry other proteins from the nucleus to other parts of the cell to keep it working.

Selinexor (Xpovio) is a drug known as a nuclear export inhibitor. It works by blocking the XPO1 protein. When the diffuse large B-cell lymphoma (DLBCL) cell cannot move proteins outside of its nucleus, the lymphoma cell dies.

This drug is used in people with DLBCL whose cancer has come back or has been treated with and no longer responds to at least 2 other DLBCL drugs.

It is a pill that is taken on the first and third day of each week.

Common side effects include feeling tired, nausea, diarrhea, loss of appetite, weight loss, vomiting, constipation, and fever. Other more serious side effects can include low platelet counts, low white blood cell counts, low blood sodium levels, infection, dizziness, and more severe gastrointestinal symptoms.