Immunotherapy for Hodgkin Lymphoma

Immunotherapy is the use of medicines to help someone’s immune system better recognize and destroy cancer cells. Immunotherapy can be used to treat some people with Hodgkin lymphoma (HL).

Monoclonal antibodies

Antibodies are proteins made by your immune system to help fight infections. Man-made versions, called monoclonal antibodies (mAbs), can be designed to attack a specific target, such as a substance on the surface of lymphocytes (the cells in which HL starts).

Brentuximab vedotin (Adcetris)

Classic Hodgkin lymphoma (cHL) cells usually have the CD30 molecule on their surface. Brentuximab vedotin is an anti-CD30 antibody attached to a chemo drug. The antibody acts like a homing signal, bringing the chemo drug to the lymphoma cells with CD30 on them. The drug enters the cells and kills them when they try to divide into new cells.

This drug can be used:

  • As the first treatment for stage III or IV cHL (where it is given along with chemotherapy)
  • In people with cHL that has come back after other treatments, including after a stem cell transplant (or in people who can't have a transplant for some reason). It can be given alone or along with chemo.
  • After a stem cell transplant for people at high risk of the cancer coming back after treatment. In this situation, it is usually given by itself for a year.

Brentuximab vedotin is infused into a vein (IV), usually every 3 weeks. Common side effects include:

  • Nerve damage (neuropathy)
  • Low blood cell counts
  • Fatigue
  • Fever
  • Nausea and vomiting
  • Infections
  • Diarrhea

Rarely, serious side effects occur during IV infusions, such as trouble breathing and low blood pressure

Rituximab (Rituxan)

Rituximab may be used to treat nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). This mAb attaches to a substance called CD20 on some types of lymphoma cells. It's often given along with chemotherapy and/or radiation therapy.

Rituximab is given as an IV infusion in the doctor’s office or clinic. When it's used by itself, it's usually given once a week for 4 weeks, which may then be repeated several months later. When it's given along with chemotherapy, it's most often given on the first day of each chemo cycle.

Common side effects are usually mild but can include:

  • Chills
  • Fever
  • Nausea
  • Rashes
  • Fatigue
  • Headaches

Rarely, more severe side effects occur during infusions, such as trouble breathing and low blood pressure. You will be given medicines before each treatment to help keep this from happening. But even if these symptoms do occur during the first infusion, it's unusual for them to happen again with later doses.

Rituximab can cause prior hepatitis B infections to become active again, which sometimes leads to severe liver problems or even death. Your doctor will probably check your blood for signs of hepatitis before starting this drug.

Rituximab can also increase your risk of infection for several months after the drug is stopped.

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoint” proteins, which act like switches on immune cells that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system.

Nivolumab (Opdivo) and pembrolizumab (Keytruda) are checkpoint inhibitors that can be used in people with classic Hodgkin lymphoma whose cancer has grown during treatment (called refractory cancer) or has returned after other treatments have been tried (called recurrent or relapsed cancer).

These drugs target PD-1, a protein on certain immune system cells (called T cells) that normally helps keep these cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

These drugs are given as an intravenous (IV) infusion, typically every 2, 3, or 6 weeks.

Possible side effects

Side effects of these drugs can include:

  • Fatigue
  • Fever
  • Cough
  • Nausea
  • Itching
  • Skin rash
  • Loss of appetite
  • Joint pain
  • Constipation
  • Diarrhea

Other, more serious side effects occur less often.

Infusion reactions: Some people might have an infusion reaction while getting one of these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting one of these drugs.

Autoimmune reactions: These drugs work by basically removing one of the safeguards on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.

If you notice any problems, you should tell your health care team about it right away. If serious side effects do occur, treatment may need to be stopped and you may get high doses of steroids to suppress your immune system.

More information about immunotherapy

To learn more about how drugs that work on the immune system are used to treat cancer, see Cancer Immunotherapy.

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.

Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311-319.

Bartlett NL, Foyil KV. Chapter 105: Hodgkin lymphoma. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa. Elsevier: 2014.

Bristol-Myers Squibb Company. OPDIVO highlights of prescribing information. 3/2018. Accessed at https://packageinserts.bms.com/pi/pi_opdivo.pdf on March 20, 2018.

Chiu J, Ernst DM, Keating A. Acquired Natural Killer Cell Dysfunction in the Tumor Microenvironment of Classic Hodgkin Lymphoma. Front Immunol. 2018;9:267.

Dada R. Program death inhibitors in classical Hodgkin's lymphoma: a comprehensive review. Ann Hematol. 2018;97(4):555-561.

Genentech, Inc. RITUXAN highlights of prescribing information. 4/2016. Accessed at www.gene.com/download/pdf/rituxan_prescribing.pdf on March 20, 2018.

Merck & Co., Inc. KEYTRUDA highlights of prescribing information. 11/2017. Accessed at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf on March 20, 2018.

National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Hodgkin Lymphoma, Version I.2018 -- December 20, 2017. Accessed at www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf on March 20, 2018.

Seattle Genetics, Inc. ADCETRIS highlights of prescribing information. 11/2017. Accessed at https://adcetris.com/themes/adcetris/assets/docs/PrescribingInformation.pdf on March 20, 2018.

Shanbhag S, Ambinder RF. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J Clin. 2018;68(2):116-132.

US Food & Drug Administration. FDA News Release: FDA expands approval of Adcetris for first-line treatment of Stage III or IV classical Hodgkin lymphoma in combination with chemotherapy. Accessed at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm601935.htm?utm_campaign=03202018_PR_Expanded%20use%20hodgin%20lymphoma%20drug&utm_medium=email&utm_source=Eloqua on March 20, 2018.

Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363:1812−1821.

Younes A, Carbone A, Johnson P, Dabaja B, Ansell S, Kuruvilla J. Chapter 102: 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.

References

Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311-319.

Bartlett NL, Foyil KV. Chapter 105: Hodgkin lymphoma. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa. Elsevier: 2014.

Bristol-Myers Squibb Company. OPDIVO highlights of prescribing information. 3/2018. Accessed at https://packageinserts.bms.com/pi/pi_opdivo.pdf on March 20, 2018.

Chiu J, Ernst DM, Keating A. Acquired Natural Killer Cell Dysfunction in the Tumor Microenvironment of Classic Hodgkin Lymphoma. Front Immunol. 2018;9:267.

Dada R. Program death inhibitors in classical Hodgkin's lymphoma: a comprehensive review. Ann Hematol. 2018;97(4):555-561.

Genentech, Inc. RITUXAN highlights of prescribing information. 4/2016. Accessed at www.gene.com/download/pdf/rituxan_prescribing.pdf on March 20, 2018.

Merck & Co., Inc. KEYTRUDA highlights of prescribing information. 11/2017. Accessed at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf on March 20, 2018.

National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Hodgkin Lymphoma, Version I.2018 -- December 20, 2017. Accessed at www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf on March 20, 2018.

Seattle Genetics, Inc. ADCETRIS highlights of prescribing information. 11/2017. Accessed at https://adcetris.com/themes/adcetris/assets/docs/PrescribingInformation.pdf on March 20, 2018.

Shanbhag S, Ambinder RF. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J Clin. 2018;68(2):116-132.

US Food & Drug Administration. FDA News Release: FDA expands approval of Adcetris for first-line treatment of Stage III or IV classical Hodgkin lymphoma in combination with chemotherapy. Accessed at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm601935.htm?utm_campaign=03202018_PR_Expanded%20use%20hodgin%20lymphoma%20drug&utm_medium=email&utm_source=Eloqua on March 20, 2018.

Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363:1812−1821.

Younes A, Carbone A, Johnson P, Dabaja B, Ansell S, Kuruvilla J. Chapter 102: 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.

Last Revised: October 29, 2020

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