Immunotherapy for Soft Tissue Sarcoma

Immunotherapy is the use of medicines to help a person’s own immune system recognize and destroy cancer cells more effectively.

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoint" proteins on immune cells or other cells that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. But drugs that target these checkpoints, known as checkpoint inhibitors, can be used to treat some people with soft tissue sarcomas.

PD-1 and PD-L1 inhibitors

PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as a type of “off switch” that helps keep the T cells from attacking other cells in the body. It does this when it attaches to PD-L1, a protein on some normal (and cancer) cells. When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them avoid being attacked by the immune cells.

Atezolizumab (Tecentriq) targets the PD-L1 checkpoint protein. By blocking PD-L1, this drug boosts the immune response against cancer cells. This can shrink some tumors or slow their growth.

Atezolizumab can be used in people with alveolar soft-part sarcoma that can’t be removed with surgery or that has spread (metastasized) to other parts of the body. 

This drug is given as an intravenous (IV) infusion, typically every 2, 3, or 4 weeks. It can also be given (as Tecentriq Hybreza) as an injection under the skin (subcutaneously) over several minutes, typically once every 3 weeks.

Pembrolizumab (Keytruda) targets the PD-1 checkpoint protein, which can also help the immune system attack the cancer cells. While this drug is not FDA-approved specifically to treat soft tissue sarcoma, it is approved to treat other cancers. Some early studies have shown it can be helpful against certain types of advanced soft tissue sarcomas, so it might be an option in some situations. It might also be an option if the sarcoma cells are found to have certain gene or protein changes.

This drug is given as an intravenous (IV) infusion, typically every 3 or 6 weeks.

Possible side effects of checkpoint inhibitors

Side effects of these types of drugs can include fatigue, cough, nausea, itching, skin rash, loss of appetite, constipation, joint pain, and diarrhea.

Other, more serious side effects occur less often.

Infusion reactions: Some people might have an infusion reaction while getting one of these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting one of these drugs.

Autoimmune reactions: These drugs work by basically removing one of the safeguards on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.

It’s very important to report any new side effects to your health care team as soon as possible. If serious side effects do occur, treatment may need to be stopped and you may get high doses of corticosteroids to suppress your immune system.

Autologous T cell immunotherapy

In this treatment, immune cells called T cells are removed from the patient’s blood and altered in the lab to have specific receptors (called T cell receptors, or TCRs) on their surface. These receptors can attach to certain proteins on the surface of cancer cells. The T cells are then multiplied in the lab and given back into the patient’s blood, where they can seek out the cancer cells and help launch a precise immune attack against them.

Afamitresgene autoleucel (Tecelra, also known as afami-cel) is a T cell immunotherapy that targets the MAGE-A4 protein found on some people’s cancer cells. It is approved to treat some adults with advanced synovial sarcoma who have already received chemo. People need to have their blood and tumor cells tested to see if they are eligible for this treatment. 

The treatment is given as a one-time infusion into a vein (IV), typically about 6 weeks after the T cells are first collected. You will get chemo for several days in the week before getting this treatment, which helps it work better.

Side effects of autologous T cell immunotherapy

Because this treatment can have serious side effects, it needs to be given in a medical center that has special training with this type of treatment.

This treatment can sometimes cause cytokine release syndrome (CRS), in which immune cells in the body release large amounts of chemicals into the blood. Symptoms of this life-threatening syndrome can include fever, chills, headache, nausea and vomiting, trouble breathing, very low blood pressure, a very fast heart rate, swelling, diarrhea, feeling very tired or weak, and other problems.

This treatment can sometimes cause serious neurological (nervous system) problems, such as confusion, trouble speaking, seizures, tremors, or changes in consciousness.

Some people might have an infusion reaction while getting this drug. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing.

Other serious side effects of this treatment can include serious infections, low blood cell counts (which can last for several weeks), and an increased risk for other cancers.

Other possible side effects include:

• Nausea and vomiting
• Feeling very tired
• Diarrhea or constipation
• Fever 
• Belly pain
• Trouble breathing
• Loss of appetite
• Low blood pressure
• Back pain
• Fast heart rate
• Chest pain
• General body swelling

Because of the risk of side effects, you’ll be watched closely at the medical center, typically daily for at least 7 days after the infusion.