Lymphoma
Lymphoma treatment is quickly evolving for both non-Hodgkin lymphoma and Hodgkin lymphoma. The most recent lymphoma treatments focus on improving drug precision. Treatments like targeted therapies and immunotherapy make it possible to directly focus on specific types of cells and even specific abnormalities within the cells to stop the growth of cancer.
NHL, or non-Hodgkin lymphoma, is a diverse group of cancers with different characteristics and types of cancer cells.
- Lymphocytes are white blood cells produced in the bone marrow.
- B lymphocytes, or B cells, make antibodies that fight infections.
- T lymphocytes, or T cells, help B cells make antibodies that fight infections.
- NK cells attack cancer cells and viruses.
The most common type of non-Hodgkin lymphoma is the B cell type accounting for about 85% of cases. NK (natural killer) or T-cell lymphomas develop on account of abnormal T or NK cells. These cases represent about 15% of all Non-Hodgkin’s lymphoma. Within these two broad categories of non-Hodgkin lymphoma are many subtypes – some are slow-growing while others are more aggressive.
Hodgkin lymphoma, also known as HL, is cancer that begins in lymphocytes, the white blood cells responsible for immune system responses. This category of lymphoma begins when a lymphocyte (usually a B cell) becomes abnormal, with the presence of an abnormal cell called a Reed-Sternberg cell. Hodgkin’s lymphoma can develop almost anywhere in the body because of the extensive reach of the lymphatic system. Usually, Hodgkin lymphoma is first detected in a lymph node above the diaphragm, the thin muscle that separates the chest from the abdomen. But it may also be found in a group of lymph nodes.
Types of Lymphoma Treatments Available Today
Depending on the specific subtype of lymphoma, various treatments are available. Previously the primary option was chemotherapy. But cancer researchers, including our own oncologists in the Willamette Valley, have tested new treatment options for lymphomas through clinical trials including:
New Targeted Therapy Treatments for Non Hodgkin Lymphoma
Targeted therapy drugs identify and kill specific cancer cells. Because they precisely target a specific type of protein or genetic mutation, there's less damage to healthy cells than chemotherapy or radiation therapy. The category of targeted therapy is rapidly expanding as researchers learn more about the various proteins and genetic changes in cancer cells that can be treated using this type of drug.
Types of Targeted Therapy used for Non-Hodgkin Lymphoma
Kinase inhibitor therapy blocks certain proteins which kills cancer cells, or keeps them from growing. Kinase inhibitor therapies include:
- Copanlisib, idelalisib, duvelisib, and umbralisib, block P13K proteins and may help keep lymphoma cells from growing. Doctors use them to treat follicular NHLs that have not improved or have returned after treatment with at least two other therapies. Umbralisib is also used to treat marginal zone lymphoma that has relapsed or not improved with treatment.
- Ibrutinib, acalabrutinib, and zanubrutinib are types of Bruton tyrosine kinase (BTK) inhibitor therapy. They are used to treat some types of B-cell lymphomas. Acalabrutinib works by blocking an enzyme needed by the cancer to multiply and spread and is used for a second line of treatment for mantle cell lymphoma as well as for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Proteasome inhibitors are drugs that stop enzyme complexes (proteasomes) in cells from breaking down proteins that are needed for normal cell division. This is more commonly used with other types of blood cancers, but is used for non-Hodgkin lymphoma if the patient isn’t responding to other treatments.
Immunotherapy Treatments for Non-Hodgkin Lymphoma
Immunotherapy, also called biologic therapy, uses the immune system to more effectively fight cancer. The body and lab-made substances help strengthen and guide the body's natural defenses against cancer.
Monoclonal antibodies use laboratory-made proteins to treat Non-Hodgkin lymphoma. There are several monoclonal antibodies used to treat NHL including:
- Antibodies targeting CD20: The CD20 antigen is a protein on the surface of B lymphocytes that can be targeted by a number of monoclonal antibodies. This can include mosunetuzumab, epcoritamab, and glofitamab. The drugs are infused over several hours and may be used alone or in combination with other treatment methods, such as chemotherapy. There is also a method that can be given as an injection into the skin, which reduces the treatment session time from hours to minutes.
T-cell engaging bispecific antibodies are newer antibodies designed to attach to two different targets. Once in the body, one part of the antibodies attaches to the CD3 protein on immune cells called T cells. Another part attaches to a target on lymphoma cells, such as the CD20 protein. This brings the two cells together, which helps the immune system attack the lymphoma cells. - Antibodies targeting CD19: The CD19 antigen is a protein on the surface of B lymphocytes. This monoclonal antibody drug can be used along with immunomodulating drugs to treat diffuse large B-cell lymphoma (DLBCL) that has returned or is not responding to other treatments. It is infused into a vein, about once a week for the first few months, and then once every two weeks.
An antibody-drug conjugate (ADC) is a monoclonal antibody connected to a chemotherapy drug. This is when the antibody targeting CD19 acts like a signal by attaching on the CD19 protein on cancer cells calling the chemotherapy directly to them. This ADC is often used alone to treat some large B-cell lymphoma types. - Antibodies targeting CD52: This antibody is directed at the CD52 antigen and is effective treatment for some cases of SLL/CLL and peripheral T-cell lymphomas.
- Antibodies that target CD30: This ADC is targeted at CD30 protein and attached to a chemotherapy drug. This can be used to treat some T-cell lymphomas.
- Antibodies that target CD79b: This ADC is anti-CD79b attached to chemotherapy. This can be used with chemotherapy to treat diffuse large B-cell lymphoma (DLBCL).
Immune checkpoint inhibitors, another type of immunotherapy drug, work by blocking checkpoint proteins from binding with their partner proteins on cancer cells. This makes it possible for the patient’s T cells to kill cancer cells. Primary mediastinal large B-cell lymphoma that has not been stopped by at least two other treatments may be treated with pembrolizumab (Keytruda).
Chimeric Antigen Receptor (CAR)-T therapy changes the patient's immune system T cells to help them fight specific proteins on cancer cells. T cells are removed from the patient, and special receptors are added to their surface in the laboratory. After they grow in the laboratory, they’re given back to the patient by infusion (IV). The altered cells multiply in the blood, find lymphoma cells, and precisely attack them.
CAR T-cell therapy (such as axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, and brexucabtagene autoleucel) is used to treat large B-cell lymphoma that has not responded to the initial treatments with chemotherapy and immunotherapy, or for cases that have returned within a year of treatment. It may also be used for follicular lymphoma, after at least two other kinds of treatment have been tried.Brexucabtagene autoleucel, also known as brexu-cel, is specifically being used to treat mantle cell lymphoma that has returned or is not responding to treatments.
Immunomodulatory drugs impact the immune system, but we are still studying exactly how they do this. Immunomodulators influence how the immune system works, increasing its ability to fight non-hodgkin lymphoma. This therapy can influence or modulate how the immune system responds to cancer cells. Doctors use several medications to target and treat lymphoma of various types and stages.
The Latest Immunotherapy for Follicular non-Hodgkin Lymphoma
The FDA has recently approved mosunetuzumab-axgb ( Lunsumio™), a new category of immunotherapy for advanced follicular lymphoma. This bispecific antibody is the first of its kind to treat follicular lymphoma, a type of non-Hodgkin lymphoma. This subtype of non-Hodgkin lymphoma has had limited treatment options, especially when patients do not respond to other treatment methods or the lymphoma has returned. Lunsumio works by engaging B and T cells to destroy cancer cells.
Advancements in Immunotherapy for Hodgkin Lymphoma Treatments
Hodgkin lymphoma treatments are also being researched and new treatment therapies have recently been approved.
A more recent approach is the use of brentuximab vedotin (Adcetris®). This drug treats Hodgkin's by targeting CD30 protein, a marker for Hodgkin lymphoma. It can be used alone or in combination with chemotherapy and is approved for initial treatment in patients with advanced Hodgkin lymphoma. This can also be used for patients with a high risk of recurrent lymphoma after treatment.
Rituximab (Rituxan®) is another type of immunotherapy drug used for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). This IV-infused monoclonal antibody attaches to the CD20 substance on some types of lymphoma cells. It's commonly given with chemotherapy and/or radiation therapy.
This targeted therapy drug has potential to help patients avoid chemotherapy that can be toxic and difficult for older patients. Additionally, clinical trials are studying this drug in combination with chemotherapy or other immunotherapies.
The FDA has approved two other medications, nivolumab (Opdivo®) and pembrolizumab (Keytruda®), for patients with recurrent Hodgkin lymphoma after other treatments. These immune checkpoint inhibitors make it possible for the body to differentiate cancer cells from healthy cells so that the immune system can be turned on to destroy the cancer cells.
Expert Hematologists at WVCI Using The Latest to Treat Your Lymphoma
The experienced team of hematologists at Willamette Valley Cancer Institute can help you determine if new lymphoma treatments are right for you. Whether you are newly diagnosed or your lymphoma has returned after years of remission, our patient-centered care means we'll be with you every step of your cancer care journey.
Original content published December 2022. Updated December 2023.
