Lymphoma occurs when white blood cells known as lymphocytes grow abnormally. There are nearly 70 subtypes of Hodgkin lymphoma and non-Hodgkin lymphoma that have been defined. The type of immunotherapy used varies with the type of lymphoma a patient has and with other health-related factors. The U.S. Food and Drug Administration (FDA) has approved several immunotherapy agents for lymphoma and a range of potential new agents is undergoing clinical testing.
One of the main types of immunotherapy for lymphoma is “naked” monoclonal antibodies, which bind to specific proteins on lymphoma cells. Once affixed, they can destroy the cell themselves or enlist the immune system to do so. In many cases, the monoclonal antibodies are combined with chemotherapy in the treatment regimen.
Another form of immunotherapy for lymphoma is antibody-drug conjugates, in which a monoclonal antibody is attached to a chemotherapy agent. The resulting compound works like a biological smart bomb, carrying the cancer-killing chemotherapy drug directly to tumor cells. One such conjugate, brentuximab vedotin, has been approved for patients with advanced classical Hodgkin lymphoma or anaplastic large cell lymphoma.
Radioimmunotherapy works much as conjugate therapies do, but with radiation in place of chemotherapy. By attaching a monoclonal antibody to a radioactive molecule, this technique can deliver a dose of radiation therapy directly to tumor cells. The radioimmunotherapy drug ibrutumomab tiuxetan has been FDA-approved for the treatment of relapsed or resistant, low grade or follicular B-cell lymphoma.
Immunomodulatory drugs such as lenalidomide can act in a variety of ways against tumor cells – causing them to die, starving them of nutrients in the blood, and stimulating the immune system. Lenalidomide is used in patients with several types of lymphoma.
Newer immunotherapy drugs known as immune checkpoint inhibitors are designed to unshackle immune system cells from attacking tumor cells. The drugs nivolumab and pembrolizumab are both approved for advanced classical Hodgkin lymphoma.
As of May 2018, CAR T-cell therapy has been approved by the U.S. Food and Drug Administration as standard therapy for some adult patients with aggressive non-Hodgkin lymphoma that has relapsed after prior treatments, or has not responded to other therapies (refractory), and for patients age 25 and under with relapsed or refractory B-cell acute lymphoblastic leukemia. An array of other immunotherapy approaches are also being tested in clinical trials in patients with lymphoma. These include vaccines, which stimulate the immune system to fight the disease.
“Immunotherapy has a long and successful history in the treatment of lymphoma,” says Philippe Armand, MD, PhD, director of Clinical Research in the Lymphoma Program at Dana-Farber. “Today, novel agents such as checkpoint-blocking antibodies and CAR T cells have the potential to revolutionize the way we approach a number of different lymphoma types. Our research group is heavily involved in trying to better understand and define the optimal role of these treatments in the care of patients with lymphoma.”