Helpline: (800) 500-9976 Getting the Facts [email protected] Immunotherapy and Lymphoma Overview Introduction to Immunotherapy their immunotherapy in an outpatient clinic, hospital outpatient The term immunotherapy refers to treatments that help promote department, or doctor’s office. Sometimes patients havetay to in s the body’s own immune response. The immune system is made the hospital to receive their treatment. of various cells, tissues, and organs that work together toght fi off Depending on the type of lymphoma, immunotherapies may be harmful pathogens, like bacteria and viruses. When the immune used for patients with relapsed (disease returns) or refractory system is not working properly due to disease, immunotherapies (disease no longer responds to treatment) disease. Several agents may be given to restore its function. Most immunotherapies stimulate are approved by the U.S. Food and Drug Administration (FDA) for parts or all of the immune system, enabling it to once again eliminate different lymphoma subtypes, and new unapproved immunotherapy unwanted pathogens. medications and treatment regimens are being evaluated and Immunotherapy and Cancer may be given to patients in clinical trials. This fact sheet reviews The immune system normally patrols the body for cancer cells. immunotherapies that are currently used or being evaluated in the When a cancer cell is detected, the immune system launches treatment of lymphoma. an attack to eliminate it. However, some cancer cells are able to Overview of Specific Therapies “hide” from or otherwise deceive the immune system, and can grow in an uncontrolled manner, until they form tumors or spread Monoclonal Antibodies through the body (such as the case in lymphoma). Many cancers Many of the immunotherapies used to treat lymphoma are effectively shut down the immune system’s ability to eliminate them. monoclonal antibodies. Anantibody is a protein that binds to Immunotherapies help fight cancer by enhancing the immune a single type of molecule, such as another protein. Each type of system so that it can do its job and eliminate cancer cells from the antibody therefore has a unique target. Lymphoma cells have body. Immunotherapy agents have been approved for the treatment proteins on their surfaces called CD (cluster of differentiation) of many types of cancer, including lymphoma. proteins; examples include CD20 and CD52. Many of the antibodies used to treat lymphoma were designed to recognize and bind Immunotherapy and Lymphoma to these CD proteins. When they do, they either destroy the cell Immunotherapies have been used for the treatment of lymphoma directly or recruit the individual’s own immune system to destroy for decades. Lymphoma occurs when cells of the immune system lymphoma cells. Examples of FDA-approved antibodies used called lymphocytes, a type of white blood cell, grow and multiply to treat lymphoma include rituximab (Rituxan), obinutuzumab uncontrollably. The body has two main types of lymphocytes (Gazyva), and ofatumumab (Arzerra). All monoclonal antibodies that can develop into lymphomas: B lymphocytes (B cells) and T are given either intravenously or subcutaneously. Common side lymphocytes (T cells). Lymphoma cells tend to be sensitive to effects of monoclonal antibodies include allergic reactions, fever, changes in the immune system, although this differs depending chills, weakness, headache, nausea/vomiting, diarrhea, low blood on the lymphoma subtype and between patients. Ultimately, how pressure, chest tightness, and rashes. lymphomas respond to immunotherapy depends on how well the immune system can target the lymphoma cells. Rituximab (Rituxan) For the treatment of patients with: Immunotherapy as a Treatment Option • Relapsed or refractory, low-grade or follicular, CD20-positive, Background B-cell non-Hodgkin lymphoma (NHL) as a single agent Most immunotherapy drugs are given to patients in the same way as • Previously untreated follicular, CD20-positive, B-cell NHL chemotherapy–orally (pill taken by mouth), subcutaneously (injection in combination with firstline (initial) chemotherapy and, under the skin), or intravenously (injection directly into a vein). in patients achieving a complete or partial response to Immunotherapy drugs may even be given with chemotherapy, such rituximab in combination with chemotherapy, as single-agent as in the R-CHOP regimen (rituximab [Rituxan], cyclophosphamide, maintenance therapy doxorubicin, vincristine, prednisone). Patients who have received • Non-progressing (including stable disease), low-grade, catheters for chemotherapy may receive their immunotherapy CD20-positive, B-cell NHL as a single agent after firstline CVP through their catheter as well. For more information on chemotherapy (cyclophosphamide, vincristine, prednisone) chemotherapy regimens, view the fact sheet titled Getting The Facts – Chemotherapy • Previously untreated diffuse large B-cell, CD20-positive NHL on the Lymphoma Research Foundation’s (LRF’s) website at in combination with CHOP (cyclophosphamide, doxorubicin, www.lymphoma.org/publications. vincristine, prednisone) or other anthracycline-based Oncology nurses are usually responsible for administering the chemotherapy regimens immunotherapy prescribed by the doctor. Most patients receive Helpline: (800) 500-9976 [email protected] • In combination with fludarabine (Fludara) and doses of radioactivity, which is intended to kill the cell. The only cyclophosphamide (FC), for the treatment of patients with FDA-approved RIT for lymphoma is ibritumomab tiuxetan (Zevalin). previously untreated and previously treated CD20-positive RIT is given intravenously. Side effects of RIT include fever/chills, chronic lymphocytic leukemia (CLL) pneumonia, lung inflammation, arrhythmias, and low blood counts. Obinutuzumab (Gazyva) Ibritumomab Tiuxetan (Zevalin) • In combination with chlorambucil (Leukeran) for the treatment • For the treatment of relapsed or refractory, low-grade or of patients with previously untreated CLL follicular B-cell NHL • In combination with bendamustine (Treanda) followed by • For the treatment of previously untreated follicular NHL in obinutuzumab monotherapy for the treatment of patients with patients who achieve a partial or complete response to firstline follicular lymphoma (FL) who relapsed after, or are refractory chemotherapy to, a rituximab (Rituxan)-containing regimen Cytokines Ofatumumab (Arzerra) Cytokine drugs, such as interferon alfa-2b (Intron A) and denileukin • In combination with chlorambucil, for the treatment of diftitox (Ontak), are synthetic versions of naturally occurring previously untreated patients with CLL for whom fludarabine cytokines (proteins used by immune system cells to communicate (Fludara)-based therapy is considered inappropriate with each other). They are not commonly used today for the treatment of lymphoma. Cytokine drugs boost the body’s immune • In combination with fludarabine and cyclophosphamide for the response to lymphoma cells. They may be given subcutaneously treatment of patients with relapsed CLL or intravenously. Common side effects of cytokines include u-likefl For extended treatment of patients who are in complete or • symptoms, low white cell counts, rashes, and thinning hair. partial response after at least two lines of therapy for recurrent or progressive CLL Interferon Alfa-2b (Intron A) For the initial treatment of clinically aggressive follicular NHL • For the treatment of patients with CLL refractory to fludarabine • in conjunction with anthracycline-containing combination and alemtuzumab (Campath) chemotherapy in patients 18 years of age or older Antibody-Drug Conjugates Denileukin Diftitox (Ontak) An antibody-drug conjugate (ADC) is a monoclonal antibody For the treatment of patients with persistent or recurrent attached to a chemotherapy drug. These agents target lymphoma • cutaneous T-cell lymphoma whose malignant cells express cells by attaching to a protein on the cell surface, such as CD30. The the CD25 component of the IL-2 receptor ADC then enters the cell, where the chemotherapy drug separates from the antibody portion and kills the cell by targeting a critical Immunomodulatory Drugs cell function, such as cell division. Similar to monoclonal tibodies,an Immunomodulatory drugs (IMiDs), such as lenalidomide (Revlimid), ADC is given intravenously. An example of an FDA-approved ADC have many ways of working against tumor cells. They cause tumor is brentuximab vedotin (Adcetris). Side effects are causedoth b by cells to die, help keep tumors from getting nutrients from the blood, the antibody and the chemotherapy portion of the drug, and may and stimulate the immune system. This drug is given orally, in include low blood cell counts, nerve damage leading to neuropathy, capsule form. The most common side effects of lenalidomide are anemia, fatigue, and nausea. low blood cell counts, fatigue, diarrhea, nausea, cough, fever, rash, Brentuximab Vedotin (Adcetris) shortness of breath, itching, constipation, and swelling. • For the treatment of patients with classical Hodgkin lymphoma Lenalidomide (Revlimid) (HL) after failure of autologous hematopoietic stem cell • Treatment of patients with mantle cell lymphoma (MCL) whose transplantation (auto-HSCT) or after failure of at least two disease has relapsed or progressed after two prior therapies, prior multi-agent chemotherapy regimens in patients who are one of which included bortezomib (Velcade) not auto-HSCT candidates Checkpoint Inhibitors • For the treatment of