Doctors treat all diseases according to the “standard of care.” That’s the approach that the medical community agrees is the best way to start treatment for this particular condition. As with many other conditions, there is no single standard of care for follicular lymphoma. Instead, many treatment options are available. The one that is right for you will depend on many things.
Some people start treatment right away. Others go through a “watch and wait” period during which doctors closely monitor disease progress to decide when to start treatment. Once treatment starts, doctors have many medications and strategies to choose from. They may use one or a combination.
Most people progress through many medications. Usually, one treatment approach can keep the cancer at bay for a while. Then, if the cancer comes back again, you move on to the next approach.
Here’s an overview of the many therapies available when you have follicular lymphoma – those in use for years and some of the newer choices on the market and in clinical trials.
If it’s early enough and the lymphoma is still restricted to one or two areas, doctors can aim high-dose beams of radiation right at the affected area to try to shrink or destroy the tumors. About half of people who get this treatment at this early stage are cured.
Your immune system fights many illnesses by producing proteins, called antibodies, custom-made to fend off the specific infection that has entered your body. Unfortunately, the human immune system isn’t so great at creating effective antibodies against cancer. That’s why some medications for cancer, called monoclonal antibodies, contain cancer-fighting antibodies made in a lab.
Monoclonal antibodies, called anti-CD20 antibodies, are a common form of treatment for follicular lymphoma. These lab-made antibodies target a specific protein on the surface of follicular lymphoma cells called CD20. When they latch onto and block these proteins, they can stop or slow the growth and progress of the cancer.
Rituximab (Rituxan) and obinutuzumab (Gazyva) are the most commonly used anti-CD20 drugs for follicular lymphoma. But there are others, too.
You’ll go to an infusion center to receive monoclonal antibodies through an IV. You may go one or more days a week for several weeks or months. If your cancer responds well to the drug, you may then continue to receive it, but less frequently, as maintenance therapy for an extended period of time.
Depending on your unique case, you could get antibodies alone or with chemotherapy.
Chemotherapy for Follicular Lymphoma
Depending on your symptoms, number of tumors, and overall health, your doctor may prescribe chemotherapy along with monoclonal antibodies.
Your doctor is most likely to use one of the following two chemotherapy options along with an anti-CD20 drug if you have symptoms and a high tumor burden:
- Bendamustine alone
- Cyclophosphamide, doxorubicin, vincristine, and prednisone combined
Studies show that more than 90% of people respond to rituximab plus one of these chemotherapy options. But doctors tend to prefer bendamustine over the chemo combo because it:
- Delays disease progression by an average of 70 months compared to 31 months on combination therapy.
- Does not cause the hair loss, heart and neurological problems, and other health problems that combination therapy can.
Still, combination chemotherapy may be a better fit in certain cases depending on your individual circumstances.
Stem Cell (Bone Marrow) Transplant
This procedure offers a way for you to get higher doses of chemotherapy, which may be necessary for some people, especially after a relapse. Usually, the dose of chemotherapy you can get safely is limited by the risk of damage to your bone marrow. With a stem cell transplant, you receive high-dose chemotherapy, which can wipe out more cancer cells but also your bone marrow. Then you receive new stem cells that will begin to regrow the bone marrow that was lost.
Other Non-Chemotherapy Drugs
Doctors have several other drugs at their disposal besides anti-CD20 antibodies and chemotherapy. They usually try these after you’ve had rituximab plus chemotherapy and your disease has progressed. But, in some cases, there might be a reason to try one of these drugs up front.
Either way, at some point in your care, you might hear of or try some of the following medications:
Lenalidomide. This is what’s called an immunomodulatory drug. That means it changes the way the immune system behaves. Lenalidomide blocks a protein on lymphoma cells called cereblon and also interferes with the environment around the tumor that might help the cancer cells survive.
In a study that compared rituximab alone to rituximab plus lenalidomide, the combo almost tripled the length of time before the lymphoma progressed. People on the combo treatment had no disease progression for an average of 39 months compared to 14 months on rituximab alone.
You typically take a lenalidomide pill every day for 3 weeks out of every month for up to 12 months.
PI3K inhibitors. These are targeted drugs, which means they interfere with a specific process that helps keep cancer cells alive. PI3K inhibitors interfere with the communication between cells that helps cancer cells survive. Four PI3K inhibitors have FDA approval for relapsed or treatment-resistant follicular lymphoma:
- Copanlisib (Aliqopa)
- Duvelisib (Copiktra)
- Idelalisib (Zydelig)
- Umbralisib (Ukoniq)
PI3K inhibitors are pills you take once or twice a day. About 40% to 60% of people respond to these drugs. They tend to delay disease progression for 9 to 11 months.
Tazemetostat. Cancer cells become resistant to treatment by changing or “mutating.” Tazemetostat is for people whose follicular lymphoma has relapsed a second time after developing a specific treatment-resisting gene change called an EZH2 mutation. About 1 in 4 people with follicular lymphoma have this gene change. It helps cancer cells multiply. Tazemetostat targets that mutation to stop its cancer-promoting activity.
Tazemetostat is a pill you take twice a day. About 7 in 10 people respond to it and delay disease progression for around 13 to 14 months.
Radioimmunotherapy. This treatment approach combines radiation with anti-CD20 antibodies. The IV medication is radioactive so that when the lab-made antibodies find and latch onto specific proteins on the cancer cells, they deliver radiation to the cells at the same time.
More than 85% of people who get this treatment plus rituximab respond to it. The response rate is slightly lower in people whose cancer has become resistant to rituximab.
CAR T-Cell Therapy. This type of treatment has been a breakthrough in aggressive blood cancers such as diffuse large B cell lymphoma. In this therapy, doctors remove immune cells, called T cells, from your body. They then use medication to reengineer the cells to recognize and fight cancer cells. Then they put the souped-up cells back in your body.
It’s FDA approved for relapsed or treatment-resistant follicular lymphoma, but it hasn’t been in use for as long as other treatments. So far, researchers have found that 85% to 95% of patients respond to this type of treatment depending on the specific medication used. In a study of axicabtagene (Yescarta), one specific type of CAR T-cell therapy, the treatment delayed disease progression by about 40 months.
Treatments for Follicular Lymphoma in Development
Besides the many drugs for follicular lymphoma currently on the market, researchers continue to study numerous others. Here’s a look at treatment options that may be on the horizon.
New antibodies. Rituximab targets one protein, CD20, on the surface of follicular lymphoma cells. Scientists continue to research other lab-made antibodies that would target other proteins on lymphoma cells. Some of this research explores what’s called bispecific antibodies – drugs that contain two different antibodies aimed at two different proteins.
Antibody-drug conjugates. These medications contain both a lab-made antibody and an anti-cancer drug. Lab-made antibodies can recognize and latch onto specific proteins on the surface of cancer cells in order to shut down their activity. With antibody-drug conjugates, when the medicine enters your system and latches onto the specific protein on the surface of the cancer cell, it delivers an anti-cancer drug to the cell at the same time.
Researchers are exploring a few of these types of drugs for the treatment of follicular lymphoma. In clinical trials, they are giving these drugs in combination with other drugs already in wide use for follicular lymphoma, such as rituximab and lenalidomide.
Checkpoint inhibitors. Your immune system has brakes that keep it from overreacting and firing on all cylinders at all times. Cancer cells exploit those brakes. They carry special proteins that signal to the immune system that there’s no need to attack. That way cancer cells can move about the body as they please.
Checkpoint inhibitors block those deceptive proteins and effectively release the brakes on the immune system. These drugs are already in use for the treatment of other cancers, such as advanced lung cancer. Researchers are now studying their effects, in combination with other drugs, in follicular lymphoma.
Many drugs currently in clinical trials are already approved to treat other cancers. This can sometimes cut down on the amount of time it takes for them to get FDA approval for a different cancer. That means more options could become available to more people sooner.
Photo Credit: WebMD
National Cancer Institute: “Standard of care.”
Patient Empowerment Network: “What Factors are Considered When Choosing a Follicular Lymphoma Treatment?”
American Cancer Society: “Treating B-Cell Non-Hodgkin Lymphoma,” “High-Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin Lymphoma,” “Immune Checkpoint Inhibitors and Their Side Effects.”
UpToDate: “Patient education: Follicular lymphoma in adults (Beyond the Basics).”
Cancer Network: “Follicular Lymphoma: a Focus on Current and Emerging Therapies.”
The ASCO Post: “Why Is Stem Cell Transplant So Underused in Follicular Lymphoma?”
Journal of Clinical Oncology: “AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma.”
FDA: “Highlights of prescribing information (Ukoniq).”
MedlinePlus: “Tazemetostat,” “Lenalidomide.”