Understanding the Role of CAR T-Cell Therapy in Treating Cancer

The purpose of cancer-targeting immunotherapy is to modify the immune system to recognize that the cancer is foreign to the body and needs to be attacked. This can be difficult, because the differences between cancer cells and healthy cells are often quite small and hard to detect.

In addition to CAR T-cell therapy, immunotherapy approaches fall into the following main categories:

• Checkpoint inhibitors are designed to block “immune checkpoint” molecules that shield cancer cells. These drugs are designed to remove the shield so that the immune system can attack cancer cells.

• Monoclonal antibodies are lab-generated proteins that target specific tumor antigens (substances that the immune system sees as being foreign or dangerous). Some monoclonal antibodies help the immune system recognize and destroy cancer cells.

• Bispecific antibodies are lab-generated proteins that target specific tumor antigens (as do monoclonal antibodies) but also bind proteins on the surface of T-cells. This allows the T-cells to get close to and destroy the cancer cells.

• Therapeutic vaccines can boost the immune system and have the potential to treat cancer or prevent it from recurring (coming back) after treatment. The U.S. Food and Drug Administration (FDA) has approved vaccines for certain cancers. Additionally, a number of types of vaccines are being studied in clinical trials.

CAR T-Cell Therapy

CAR T-cell therapy is currently approved by the FDA for certain types of relapsed (recurred) or refractory (not responding to treatment) lymphomas:

• Diffuse large B-cell lymphoma
• Primary mediastinal B-cell lymphoma
• High grade B-cell lymphoma
• Transformed follicular lymphoma
• Mantle cell lymphoma

It is also approved for the treatment of acute lymphoblastic leukemia in patients up to age 25 and, as of March 2021, for the treatment of relapsed or refractory multiple myeloma.

Based on a person’s individual circumstances, CAR T-cell therapy may be conducted on an outpatient basis or require a hospital admission. The process is similar regardless of the drug used or the specific type of cancer:

• Blood is drawn from the patient via an intravenous catheter (a flexible tube).
• T-cells are isolated from the rest of the blood.
• In a laboratory, the T-cells are genetically re-engineered by adding a chimeric antigen receptor to their surface.
• The modified T-cells (which are now CAR T-cells) are expanded to number in the hundreds of millions.
• The CAR T-cells are infused back into the patient where they target and destroy cancer cells.

The following chimeric antigen receptors are approved by the FDA:

• Axicabtagene ciloleucel (Yescarta) for the treatment of certain types of B-cell lymphoma.
• Tisagenlecleucel (Kymriah) for the treatment of certain types of B-cell lymphoma and for the treatment of acute lymphoblastic leukemia in patients up to age 25.
• Brexucabtagene autoleucel (Tecartus) for the treatment of mantle cell lymphoma.
• Lisocabtagene maraleucel (Breyanzi) for the treatment of large B-cell lymphoma.
• Idecabtagene vicleucel (Abecma) for the treatment of multiple myeloma after four or more prior lines of therapy.
• Ciltacabtagene autoleucel (Carvykti), also for the treatment of multiple myeloma after four or more prior lines of therapy.

Managing Digestive Tract Symptoms

Nausea and vomiting

• Avoid food with strong odors, as well as overly sweet, greasy, fried or highly seasoned food.
• Eat meals that are chilled, which often makes food more easily tolerated.
• Nibble on dry crackers or toast. These bland foods are easy on the stomach.
• Having something in your stomach when you take medication may help ease nausea.

Constipation

• As hydration is important to avoid constipation, make sure to drink plenty of fluids. Also, limit your intake of caffeine and alcoholic beverages, as they can cause dehydration.
• Include foods high in fiber in your daily diet, such as fruit (especially pears and prunes), vegetables and cereals. If your health care team approves, you may want to add synthetic fiber to your diet, such as Metamucil, Citrucel or FiberCon.
• Be as physically active as you can, after checking with your health care team on the level of physical activity that is right for you.
• If your doctor has prescribed a “bowel regimen,” make sure to follow it exactly.

Diarrhea

• Drink plenty of water. Ask your doctor about using drinks such as Gatorade which provide electrolytes. Electrolytes are body salts that must stay in balance for cells to work properly.
• Over-the-counter medicines such as loperamide (Imodium A-D and others) and prescription drugs are available for diarrhea but should be used only if necessary. If the diarrhea is bad enough that you need medicine, discuss it with your doctor or nurse.
• Choose fiber-dense foods such as whole grains, fruits and vegetables, all of which help form stools.
• Avoid food high in refined sugar and those sweetened with sugar alcohols such as sorbitol and mannitol.

Managing Loss of Appetite

• Eating small meals throughout the day is an easy way to take in more protein and calories, which will help maintain your weight. Try to include protein in every meal.
• To keep from feeling full early, avoid liquids with meals or take only small sips (unless you need liquids to help swallow). Drink most of your liquids between meals.
• Keep high-calorie, high-protein snacks on hand such as hard-boiled eggs, peanut butter, cheese, ice cream, granola bars, liquid nutritional supplements, puddings, nuts, canned tuna or trail mix.
• If you are struggling to maintain your appetite, talk to your health care team about whether appetite-building medication could be right for you.

Managing Fatigue

Fatigue (extreme tiredness not helped by sleep) is one of the most common side effects of many cancer treatments. Here are a few tips that may help reduce fatigue:

• Take several short naps or breaks during the day.
• Take short walks or do some light exercise, if possible.
• Try easier or shorter versions of the activities you enjoy.
• Ask your family or friends to help you with tasks you find difficult or tiring.
• Save your energy for things you find most important.

There are also prescription medications that may help. Your health care team can provide guidance on whether medication is the right approach for your individual circumstances.

Fatigue can be a symptom of other illnesses, such as anemia, diabetes, thyroid problems, heart disease, rheumatoid arthritis or depression. Be sure to ask your doctor if they think any of these conditions may be contributing to your fatigue.

It can also be beneficial to speak with an oncology social worker or oncology nurse to help manage your fatigue. These professionals can work with you to manage any emotional or practical concerns that may be causing symptoms and help you find ways to cope.

Managing Flu-Like Symptoms

The fever and aches that may occur with immunotherapy treatments can be managed with a combination of rest and medication. Acetaminophen (such as Tylenol) is often a doctor’s first choice to treat these symptoms. Nonsteroidal anti-inflammatory drugs (NSAIDs) can also help, but should be taken only if recommended by your doctor, as they can cause other side effects. NSAIDs include aspirin, ibuprofen (Motrin and others) and naproxen (Naprelan, Midol, Aleve and others).

Q: What questions should I ask my oncologist about CAR T-cell therapy as a possible treatment approach?

A: Specific questions to discuss with your oncologist include:

• Does CAR T-cell therapy have a role in treating my type of cancer, alone or in combination with other treatments?
• Is there an FDA-approved CAR T-cell therapy for my type of cancer?
• Is there anything I need to do to prepare for CAR T-cell therapy?
• Will I have to stay in the hospital for any period of time?
• Will receiving CAR T-cell therapy have an effect on future treatment decisions?
• What side effects am I most likely to experience?
• How will the effectiveness of the CAR T-cell therapy be monitored?

Q: What research is currently being conducted on CAR T-cell therapy?

A: There are a number of areas of CAR T-cell therapy research, including:

• Using CAR T-cell therapy as a treatment approach for other types of cancer.
• Collecting T-cells from donors, which eliminates one step in the process for the patient.
• Creating CAR T-cells inside the body.
• Developing CAR T-cells that have “off switches” to help limit side effects.
• Using gene-editing technology to more precisely engineer the T-cells.
• Combining chimeric antigen receptors with other immunotherapies.

Q: What is a treatment summary and why is important?

A: Keeping your own records up-to-date in the form of a treatment summary can be helpful, as it allows you and your family members to have instant access to the specifics of your cancer diagnosis and treatment. A treatment summary should include:

• Your name and date of birth.
• Date of diagnosis.
• Prescribed therapy/therapies, including dates started and stopped and dosages when appropriate.
• Dates and types of baseline and post-diagnosis testing and the results of these tests.
• Other medications and supplements you are taking.
• Names, affiliations and contact information of all members of your health care team.

Ask the members of your health care team what they suggest be included. Take your personal record with you when you visit any doctor, not just your oncologist.