Immunotherapy in Lymphoma - Lymphoma Research FoundationThe term “immunotherapy” (also called immune-oncology) refers to treatments that interact with the immune system.  The purpose of the immune system is to eliminate harmful pathogens, like bacteria and viruses, as well as cancer cells from the body.  However, in many cancers, including lymphoma, the immune system doesn’t work properly, which allows the cancer cells to grow and spread.

Lymphoma is characterized by the uncontrolled growth of abnormal immune system cells (T cells or B cells), which travel through the body.  Some of the immunotherapy drugs used in lymphoma are designed to recognize unique proteins on the surface of lymphoma cells.  These drugs become attached tot he lymphoma cells, enabling them immune system to find and destroy them.  Other immunotherapy drugs prevent lymphoma cells from suppressing the immune system, thereby restoring the immune system’s ability to destroy them.  Ultimately, how lymphomas respond to immunotherapy depends on how well the immune system can target the lymphoma cells.

Immunotherapy Types

Monoclonal antibodies are the most common biologic agents used for lymphoma therapy. Antibodies produced by our immune system recognize and destroy “foreign” invaders such as bacteria and viruses. Scientists can now produce monoclonal antibodies in the laboratory that are designed to recognize antigens (specific molecules) that are present on the surface of certain cancer cells. Once in the bloodstream, monoclonal antibodies travel throughout the body and attach themselves to their specific target antigens. Approved monoclonal antibodies include:

  • Rituximab (Rituxan)
  • Ibritumomab Tiuxetan (Zevalin)
  • Ofatumumab (Arzerra)
  • Obinutuzumab (Gazyva)
  • Alemtuzumab (Campath)
  • Brentuximab Vedotin (Adcetris)

Antibody-Drug Conjugates (ADC) is a monoclonal antibody attached to a chemotherapy drug. These agents target lymphoma cells by attaching to a protein on the cell surface, such as CD30. The ADC then enters the cell, where the chemotherapy drug separates from the antibody portion and kills the cell by targeting a critical cell function, such as cell division. Similar to monoclonal antibodies, ADC is given intravenously. An example of an FDA-approved ADC is brentuximab vedotin (Adcetris). Side effects are caused both by the antibody and the chemotherapy portion of the drug, and may include low blood cell counts, nerve damage leading to neuropathy, anemia, fatigue, and nausea. Approved antibody-drug conjugates include:

  • Brentuximab Vedotin (Adcetris)
  • Loncastuximab Tesirine-lpyl (ZYNLONTA)

Radioimmunotherapy (RIT) consists of a monoclonal antibody attached to a source of radiation. RIT acts as a “guided missile” to destroy lymphoma cells by attaching to a specific molecule on the surface of the lymphoma cell, such as CD20, and delivering small doses of radioactivity, which is intended to kill the cell. The only FDA-approved RIT for lymphoma is ibritumomab tiuxetan (Zevalin). RIT is given intravenously. Side effects of RIT include fever/chills, pneumonia, lung inflammation, arrhythmias, and low blood counts. Approved radioimmunotherapies include:

  • Ibritumomab Tiuxetan (Zevalin)

To learn more about radioimmunotherapy, download the Radioimmunotherapy Fact Sheet.

Cytokines drugs, such as interferon alfa-2b (Intron A) and denileukin diftitox (Ontak), are synthetic versions of naturally occurring cytokines (proteins used by immune system cells to communicate with each other). They are not commonly used today for the treatment of lymphoma. Cytokine drugs boost the body’s immune response to lymphoma cells. They may be given subcutaneously or intravenously. Common side effects of cytokines include flu-like symptoms, low white cell counts, rashes, and thinning hair. Approved cytokines include:

  • Interferon Alfa
  • Denileukin Diftitox (Ontak)

Immunomodulatory Drugs are treatments that have many ways of working against tumor cells. Approved immunomodulatory drugs include:

  • Lenalidomide (Revlimid)

Checkpoint Inhibitors are a new class of immunotherapy that block signaling through checkpoints, which are used by some cancers to evade detection by the immune system. Approved checkpoint inhibitors include:

  • Nivolumab (Opdivo)
  • Pembrolizumab (Keytruda)

CAR-T Cell Therapy includes the chimeric antigen receptor (CAR) T cell therapies. These directly provide engineered molecules called chimeric antigen receptors (CARs) that recognize and destroy antigens present on the surface of lymphoma cells. T cells are removed from patients and genetically modified to produce CARs. The genetically engineered CAR-T cells are grown in the laboratory until they number in the billions and are then infused back into the patient. Approved CAR-T Cell therapies include:

  • Axicabtagene Ciloleucel (Yescarta)
  • Tisagenlecleucel (Kymriah)

To learn more about CAR-T cell therapy, visit the CAR-T Cell Learning Center.

To learn more about immunotherapy and therapies under invesigation, download the Immunotherapy Fact Sheet.