Types of Immunotherapy for Lymphoma

Your specialist may talk to you about using immunotherapy to help treat your lymphoma. It’s a new type of cancer treatment that works with your natural immune system to find and kill cancer cells in your body.
These are the different kinds of immunotherapy you may get for lymphoma:

• Monoclonal antibodies
• Immunomodulating drugs
• Immune checkpoint inhibitors
• CAR T-cell therapy

Monoclonal Antibodies

Your doctor will get your lymphoma cells tested to see if they have certain markers -- proteins called antigens. You’ll get a monoclonal antibody drug that aims at the antigens found on your lymphoma cells.
Monoclonal antibodies are made in a lab. They’re designed to lock onto certain antigens that cancer cells make too much of. This means that they affect mostly cancer cells with little damage to normal cells.
Monoclonal antibodies can work in -
 1. They keep cancer cells from growing by blocking signals sent out by the cancer cells. Blocking the signals stops these processes of the cancer cells growing.

2. They can also bind to the cancer cells and trigger your immune system to kill them. They may do this by marking the cells so your immune system attacks them. Or they can block the signals the cancer cells send out to tell your immune system to leave them alone.

3. Monoclonal antibodies can be attached to toxins, chemo, or radioactive substances. They then carry these cell-killing materials to the cancer cells and lock onto the antigen. This leads to the death of the cancer cells, with little to no effect on your normal cells that don’t have the antigen.

Here are some of the ways monoclonal antibodies can be used, depending on the type of lymphoma you have:
Follicular lymphoma: If you have a large stage I or II, or a certain kind of stage III or IV follicular lymphoma, your first treatment will likely be rituximab and chemo. You might get radiation, too. Then, if the lymphoma shrinks or goes away, you may get rituximab alone as maintenance therapy.
You can get rituximab alone or along with different chemo if the lymphoma comes back after treatment or stops responding to the treatment you’re getting.
Ibritumomab (Zevalin) or obinutuzumab (Gazyva) are other monoclonal antibodies you might get instead of rituximab.

Mantle call lymphomas: You might get rituximab along with chemo as the first treatment for mantle cell lymphoma. You can also get rituximab as maintenance treatment or if the lymphoma comes back.

Diffuse large B-cell lymphoma: You will get rituximab along with chemo for any stage of diffuse large B-cell lymphoma (DLBCL). You may also get radiation afterward.
You may get a monoclonal antibody called pembrolizumab (Keytruda) if the lymphoma comes back or doesn’t respond to the treatment with rituximab.

Burkitt lymphoma: Doctors can use rituximab to treat Burkitt lymphoma as your first treatment or as a later treatment. You’ll get it along with chemo.

Marginal zone lymphomas: Both gastric and non-gastric MALT lymphomas can be treated with rituximab. So can nodal and splenic marginal zone lymphomas. If you have any stage of one of these cancers, you might get rituximab, often along with chemo, as one of your treatments. You may also get it if the cancer comes back.

Rituximab, alone or with chemo, might be the first treatment you get for lymphoma in your skin (cutaneous B-cell lymphoma). Doctors can also combine it with the drug hyaluronidase (this is called Rituxan Hycela) and give it as a shot right into the skin lymphoma if it’s only in one area.

You might get a different monoclonal antibody, brentuximab vedotin (Adcetris), by IV if other treatments haven’t worked. Alemtuzumab (Campath) is another option if the lymphoma comes back after other treatments. You might get it by IV or as a shot into the skin lymphoma.

Hodgkin's lymphoma: You may get a monoclonal antibody called brentuximab vedotin (Adcetris) if you can’t have a stem cell transplant or classic Hodgkin's lymphoma comes back after treatment. You might get this as part of your first treatment if you have certain symptoms and blood test results. This drug binds to the CD30 antigen, which is common on Hodgkin's lymphoma cells. It’s attached to a chemo drug, which then kills the cell.

You can get rituximab along with chemo and radiation if you have early stage nodular lymphocyte predominant Hodgkin's disease (NLPHD) that’s causing symptoms or large tumors. You can also get it if you have more advanced-stage NLPHD, either alone or with chemo, and maybe radiation.

T-cell lymphomas: If your lymphoma stops responding to chemo, your doctor may talk to you about trying the monoclonal antibody called alemtuzumab (Campath) or brentuximab vedotin (Adcetris).

Immunomodulating Drugs

These drugs help your immune system work better, but doctors don’t know exactly how they work. The two drugs used are thalidomide (Thalomid) and lenalidomide (Revlimid).
You may get one of these drugs if you have one of these types of non-Hodgkin's lymphoma (NHL): a T-cell lymphoma; or a follicular, marginal zone, mantle cell, or diffuse large B-cell lymphoma. You might also get one of these drugs if you have Hodgkin's lymphoma that hasn’t responded to other treatments or that came back after treatment.
You can only get these drugs if you agree to take special precautions to prevent pregnancy because they cause severe birth defects.

Immune Checkpoint Inhibitors

Cells have proteins on them called checkpoints. They help your immune system know the difference between good and bad cells. Lymphoma cells can make these checkpoints and trick your immune system into not killing them. These drugs help keep this from happening.
For example, PD-1 is a checkpoint on your T cells. When it binds to the protein called PD-L1 on another cell, the T cell is stopped from killing that cell. Your Hodgkin's lymphoma cells may make a lot of PD-L1. This tells your T cells to leave them alone. There are drugs that can block PD-1. This means your T cells aren’t turned off and your immune system can attack the cancer cells.

Classic Hodgkin's lymphoma: If the lymphoma has continued to grow while you’re getting other treatment that includes a monoclonal antibody, nivolumab (Opdivo) may be an option.
If you have a stage III or IV Hodgkin's lymphoma that’s not responding to chemo or monoclonal antibodies, or has come back after a transplant, nivolumab or pembrolizumab (Keytruda) might be helpful.

CAR T-Cell Therapy

This is a very new treatment used for some types of B-cell lymphoma. CAR stands for chimeric antigen receptor. CARs are designed to lock onto antigens found on your lymphoma cells. Each patient has their own CAR T cells made just for them.

To do this, you get some T cells filtered out of your blood to make CARs in a lab. These cells are multiplies and injected back, so that the CAR T cells travel through your blood to find, lock onto, and kill the cancer cells. They continue to grow and multiply in your body so that CAR T cells can go on to kill cancer cells for months, or maybe even years.

Your doctor may talk to you about CAR T-cell therapy if you have diffuse large B-cell lymphoma (DLBCL) that’s not responding to other treatments. It’s also approved to treat relapsed or refractory primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

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