Targeted Therapy Drugs 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 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) inhibitors

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

Romidepsin (Istodax) can be used to treat both peripheral and skin T-cell lymphomas. It is usually given after at least one other treatment has been tried. This drug is given as an IV infusion, usually once a week for 3 weeks in a row, followed by a week off.

Side effects tend to be mild, but can include lowered blood cell counts and effects on heart rhythm.

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's tyrosine kinase (BTK) is a protein that normally helps some lymphoma cells (B cells) to grow and survive. Drugs that target this protein, known as BTK inhibitors, can be helpful in treating some types of non-Hodgkin lymphoma.

Ibrutinib (Imbruvica) blocks the BTK protein. This drug can be used to treat several types of NHL, including mantle cell lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma. It’s taken by mouth as capsules, once a day.

Common side effects include diarrhea or constipation, nausea and vomiting, fatigue, swelling, decreased appetite, and low blood counts. This drug is currently approved for use after other treatments have been tried, and it’s now being studied for use earlier in treatment.

Acalabrutinib (Calquence) and zanubrutinib (Brukinsa) are other drugs that block BTK. They are used to treat mantle cell lymphoma, after at least one other treatment has been tried. These drugs are taken by mouth as capsules, twice a day.

Common side effects are headache, diarrhea, bruising, fatigue, muscle pain, cough, rash, and low blood counts. More serious side effects can include bleeding (hemorrhage), infections, and irregular heartbeat (atrial fibrillation).

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.

Idelalisib (Zydelig) blocks the PI3K-delta protein. This drug has been shown to help treat follicular lymphoma and small lymphocytic lymphoma after other treatments have been tried. It’s taken as a pill twice a day.

Common side effects include diarrhea, fever, fatigue, nausea, cough, pneumonia, belly pain, chills, rash and low blood counts. Less often, more serious side effects can also occur.

Copanlisib (Aliqopa) is another drug that blocks PI3K. It can be used to treat follicular lymphoma that comes back 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 has been shown to help treat follicular lymphoma and small lymphocytic lymphoma 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, 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.

More information about targeted therapy

To learn more about how targeted drugs are used to treat cancer, see Targeted Cancer Therapy.

To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Freedman AS, Jacobson CA, Mauch P, Aster JC. Chapter 103: Non-Hodgkin’s lymphoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.

National Cancer Institute. Physician Data Query (PDQ). Adult Non-Hodgkin Lymphoma Treatment. 2018. Accessed at https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq on May 3, 2018.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: B-cell Lymphomas. Version 3.2018. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf     on May 2, 2018.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 5.2018. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf   on May 2, 2018.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: T-cell Lymphomas. Version 3.2018. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf   on May 2, 2018.

Roschewski MJ, Wilson WH. Chapter 106: Non-Hodgkin Lymphoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa: Elsevier; 2014.

Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369:507-516.

References

Freedman AS, Jacobson CA, Mauch P, Aster JC. Chapter 103: Non-Hodgkin’s lymphoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.

National Cancer Institute. Physician Data Query (PDQ). Adult Non-Hodgkin Lymphoma Treatment. 2018. Accessed at https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq on May 3, 2018.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: B-cell Lymphomas. Version 3.2018. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf     on May 2, 2018.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 5.2018. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf   on May 2, 2018.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: T-cell Lymphomas. Version 3.2018. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf   on May 2, 2018.

Roschewski MJ, Wilson WH. Chapter 106: Non-Hodgkin Lymphoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa: Elsevier; 2014.

Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369:507-516.

Last Revised: June 23, 2020

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