Immunotherapy is changing the way we treat lymphoma. This type of therapy works with your immune system — your body’s natural protection against disease. It helps find and kill cancer cells in new ways. For some, it also offers new hope when other treatments haven’t worked.

In this article, we’ll discuss a few key points to know about immunotherapy for lymphoma. We’ll explain how it works and the different types you may hear about. Finally, you’ll learn about the potential side effects and how to get involved in clinical trials.

1. How Immunotherapy Works

Cancer immunotherapy provides a focused way of treating lymphoma. It does this by guiding certain immune cells to pay closer attention to cancer cells. Certain types of blood cancers can sometimes “hide” from the immune system or send signals that slow it down. Some types of immunotherapy help block these signals so the immune system can remain active and alert. Other types work by marking cancer cells, making them easier for immune cells to find and destroy. In summary, immunotherapy can:

• Help immune cells spot lymphoma cells more clearly
• Strengthen the immune system’s ability to attack cancer cells
• Block the signals cancer cells use to slow down immune responses
• Support long-lasting protection by helping the immune system better remember cancer cells

Immunotherapy guides certain immune cells to pay closer attention to cancer cells.

2. Types of Immunotherapy To Know About

Immunotherapy comes in several forms, and each one supports the immune system in a different way. Some immunotherapy drugs rely on lab-made antibodies (immune system proteins). Others guide your T cells (a type of white blood cell) to attack cancer more directly. Your healthcare team will choose the best option for you based on your type of lymphoma and what treatment options you’ve tried already.

Targeted Antibodies

Targeted antibodies are lab-made proteins that act like the natural antibodies your body uses to fight infections. These medicines are designed to look for certain markers on lymphoma cells. Once they attach to these markers, they can help your immune system notice and attack the cancer. Different types of targeted antibodies work in different ways.

Monoclonal antibodies attach to cancer cells and block signals that help them grow. They can also signal to immune cells for additional help in destroying the cells. Monoclonal antibodies include:

• Mogamulizumab (Poteligeo) — Used to treat two rare forms of non-Hodgkin lymphoma (NHL): Sézary syndrome and mycosis fungoides
• Obinutuzumab (Gazyva) — Approved for some blood cancers, including follicular lymphoma and chronic lymphocytic leukemia
• Rituximab (Rituxan) — Approved for CD20-positive NHL and leukemia
• Tafasitamab-cxix (Monjuvi) — Used to treat diffuse large B-cell lymphoma (DLBCL) and approved by the U.S. Food and Drug Administration (FDA) to treat relapsed or refractory (treatment-resistant) follicular lymphoma in combination with lenalidomide and rituximab

Antibody-drug conjugates (ADCs) attach an anticancer drug to an antibody. This helps deliver the drug straight to cancer cells. Examples include:

• Brentuximab vedotin (Adcetris) — Approved for people with some types of Hodgkin or non-Hodgkin lymphoma
• Loncastuximab tesirine (Zynlonta) — Used to treat some people with relapsed or refractory large B-cell lymphoma
• Polatuzumab vedotin (Polivy) — Used to treat some cases of NHL

CD20xCD3 bispecific antibodies are a new type of targeted antibody. “Bispecific” means the antibody can attach to two different targets at the same time. In this case, the drug attaches to CD20 (a marker on B-cell lymphoma cells) and CD3 (a T-cell marker). By bringing the two together, the T cell can kill the lymphoma cell more directly. FDA-approved examples include:

• Epcoritamab-bysp (Epkinly) — For relapsed or refractory DLBCL or some B-cell lymphomas, and for use in combination with lenalidomide and rituximab for relapsed or refractory follicular lymphoma
• Glofitamab-gxbm (Columvi) — For some relapsed or refractory large B-cell lymphomas
• Mosunetuzumab-axgb (Lunsumio) — For relapsed or refractory follicular lymphoma

Immunomodulators

Immunomodulators can either stimulate or suppress the immune system. Some make immune cells more active. Others block signals that cancer cells use to weaken or confuse the immune system.

Immune checkpoint inhibitors are one type of immunomodulator. They help T cells attack cancer with more strength. These drugs block “checkpoints,” which are proteins that act like brakes on the immune system. Some drugs target a checkpoint called CTLA-4, while others block PD-1 or PD-L1. These proteins help some tumor cells evade T cells. When the brakes are turned off, T cells can find and kill cancer cells more easily. Examples include:

• Nivolumab (Opdivo) — Approved for some people with Hodgkin lymphoma
• Pembrolizumab (Keytruda) — Used to treat some cases of Hodgkin lymphoma

Another immunomodulator is the R2 regimen, which combines lenalidomide (Revlimid) with rituximab. Lenalidomide helps boost immune cell activity, while rituximab targets B-cell lymphoma cells. This drug combination is FDA-approved for previously treated follicular lymphoma and marginal zone lymphoma.

Adoptive Cell Therapy

Adoptive cell therapy uses your own T cells to help fight lymphoma. T cells are first taken from your blood and sent to a lab. Then they’re “trained” to find cancer cells more easily. Once they’re ready, the cells are put back into your body to help attack the cancer.

Adoptive cell therapy uses your own T cells to help fight lymphoma.

CAR T-cell therapy is a common type of adoptive cell therapy. CAR stands for chimeric antigen receptor — a special tool added to T cells. This tool helps the cells stick to lymphoma cells and kill them more directly. FDA-approved CAR T-cell therapies include:

• Axicabtagene ciloleucel (Yescarta) — Used for certain types of large B-cell lymphoma, follicular lymphoma, and as a second-line treatment for large B-cell lymphoma
• Brexucabtagene autoleucel (Tecartus) — Approved for mantle cell lymphoma
• Liscocabtagene maraleucel (Breyanzi) — Approved for large B-cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL), follicular lymphoma, and mantle cell lymphoma
• Tisagenlecleucel (Kymriah) — Approved for large B-cell lymphoma and relapsed or refractory follicular lymphoma

3. Potential Side Effects of Immunotherapy

Like many cancer treatments, immunotherapy drugs can cause side effects. However, the exact side effects you may experience depend on the specific drug you receive and your type of cancer. Common side effects of immunotherapy drugs include:

• Fever or chills
• Fatigue (extreme tiredness that doesn’t improve with rest)
• Skin reactions, such as rash or itchiness
• Nausea
• Headaches
• Body aches
• Shortness of breath
• Changes in blood pressure
• Other flu-like symptoms

In addition, some immune checkpoint inhibitors may lead to immune-related side effects. These can include inflammation in organs such as:

• Lungs
• Colon or intestines
• Thyroid
• Kidneys
• Liver

Some immunotherapies can cause more serious reactions. CAR T-cell therapy and CD20xCD3 antibodies can cause cytokine release syndrome (CRS). This can feel like a sudden and intense bout of the flu. These therapies can also cause a condition known as immune effector cell-associated neurotoxicity syndrome (ICANS). This is a brain-related side effect that may affect speech, balance, or thinking. Your healthcare team will monitor you closely for these potential side effects during the first two weeks after you receive therapy.

4. About Clinical Trials for Lymphoma Immunotherapy

Clinical trials help doctors and researchers test new types of therapy. This allows us to learn how safe they are and how well they work. These studies can also offer access to treatments that aren’t yet approved by the FDA but may still help certain people with lymphoma. There are several types of immunotherapies currently being tested in clinical trials.

To learn more about clinical trials you may be able to participate in, talk to your oncology (cancer) team. They can help you find trials you may qualify for and discuss all the potential risks and benefits with you. You can also search online at ClinicalTrials.gov.

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