Bispecific Antibody T-Cell Engager Therapy (BsAb)

Bispecific antibody T-cell engager therapy — BsAb therapy — is a type of targeted immunotherapy that works with a patient’s immune system to find and eliminate cancer cells.

A bispecific antibody is a two-headed antibody that can bind two proteins together — one protein on a cancer cell and another protein on a T cell. T cells are part of the immune system.

Binding the two proteins together brings the T cell and the cancer cell near each other. This action acts as a locator to help T cells find cancer cell, and creates a bridge to connect them. By binding to both types of proteins, the T cell’s antitumor function is stimulated, and it releases molecules. These molecules can destroy cancer cells in several ways.

• Forcing the cancer cell to self-destruct by creating holes in it
• Stimulating the cancer cell’s surrounding target cells to display the target protein so the BsAb can identify them
• Triggering cancer cell death

Cancers Treated With BsAb T-cell Engager Therapy

The FDA has approved BsAb therapy — mainly to treat certain types of lymphoma, leukemia and multiple myeloma (blood cancers). It is also FDA-approved to treat some types of melanoma and small cell lung cancer.

• B-cell acute lymphoblastic leukemia
• Diffuse large B-cell lymphoma
• Follicular lymphoma
• Melanoma
• Multiple myeloma
• Small cell lung cancer

BsAb Therapies Offered by Our Cancer Network

The Cancer Network offers many different types of FDA-approved BsAbs and will choose the therapy that will work best for you and your cancer.

• Blinatumomab: Approved to treat B-cell acute lymphoblastic leukemia (B-ALL) in adults and children. It binds to CD19 on leukemia cells and CD3 on T cells.
• Teclistamab: Approved to treat multiple myeloma in adults when disease has returned (relapsed) or when disease does not respond or stops responding (refractory) to treatment. It binds to B-cell maturation antigens (BCMA) on myeloma cells and CD3 on T cells.
• Epcoritamab: Approved to treat diffuse large B-cell lymphoma that has come back or did not respond to treatment.
• Talquetamab: Approved to treat multiple myeloma in adults when disease has returned (relapsed) or when disease does not respond or stops responding (refractory) to treatment. It binds to GPRC5D on myeloma cells and CD3 on T cells.
• Tarlatamab: Approved to treat certain types of small cell lung cancer in adults.
• Tebentafusp: Approved to treat uveal adult melanoma that is inoperable or metastatic (has spread to other areas of the body).
• Mosunetuzumab: Approved to treat follicular lymphoma that has come back or did not respond to treatment.
• Glofitamab: Approved to treat certain types of large B-cell lymphoma that has come back or did not respond to treatment.
• Elranatamab: Approved to treat multiple myeloma that has come back or did not respond to treatment. It binds to BCMA on myeloma cells and CD3 on T cells.

Who Can Have BsAb Therapy

Your care team will carefully consider your type of cancer, previous cancer treatments, your overall health, any other medical conditions you have in addition to cancer, and your health history to decide if BsAb therapy will help you.

BsAb Insurance Coverage 

Most insurance providers cover FDA-approved immunotherapies, such as BsAb therapy. Coverage approval and rate of coverage can vary. Work with your insurance company to make sure they will authorize coverage before beginning treatment.

Why BsAb Therapy Is Not Used to Treat More Solid Tumors

Antigens (protein markers) found on the surface of solid tumor cells are also on healthy cells. Therefore, BsAb therapy can kill not only malignant cells, but also healthy cells, leading to organ damage. When new therapies are considered, the benefits of targeting protein markers to destroy cancer cells must outweigh the risks.

BsAb Therapy Is Effective in Treating Blood Cancers

BsAb therapy has been shown to be successful in treating blood cancers but some patients’ cancer stops responding to treatment after a time. Cancer cells may escape detection if they stop producing the target protein or may develop other proteins that stop T-cells from going into action.

What to Expect Before BsAb Therapy

Tests may include some or all of the following. Your doctor will also recommend all age-appropriate vaccinations before or after starting therapy, as BsAb therapy can increase your risk of serious bacterial, viral or fungal infections. 

• Blood tests
• Pregnancy test for women of child-bearing age
• Echocardiogram (ultrasound to assess heart health)
• Baseline neurological tests
• Baseline tests to assess the extent of your cancer:
  • Imaging scans
  • Bone marrow test
  • Lumbar puncture (also called spinal tap; removes a sample of cerebrospinal fluid for testing)

What Happens During BsAb Therapy

BsAb therapy is given as an injection under the skin (usually in the abdomen or thigh) or intravenously (IV), meaning through a vein. This depends on the type of BsAb your care team chooses for you. Longer-term BsAb therapy may be given IV.

For the first two or three doses, you receive a smaller amount of the drug, called a “step-up” dose, to help prevent common side effects. If there are no complications, you can receive a full dose. If side effects happen, we immediately use supportive care medications to counteract them. If there are no side effects or minimal side effects, you can return home the same day. Supportive care drugs are also available to you at home. Your medical team will continue to monitor you closely.

Your doctor may want you to have the initial “step-up” treatment in the hospital if you are an older person or have medical conditions (in addition to cancer) that may put you at higher risk of serious side effects.

While receiving outpatient therapy, you will need to live close to the hospital — within a 45-minute drive of where you receive BsAb therapy. You may be required to have quick access to emergency care during the “step-up” phase — living near or finding temporary lodging near an emergency department, in case complications arise during treatment. All Froedtert & MCW emergency departments can provide medications for side effects of BsAb therapy or side effects can be managed in the Froedtert & MCW 24-Hour Cancer Clinic.

During BsAb therapy, patients need careful monitoring:

• Vital signs
• Baseline and follow-up scores for possible neurological toxicities (side effects)
• Follow-up of fevers, including those linked with low blood pressure, dizziness or shortness of breath
• Medications to help control toxicities (side effects), as needed

When receiving BsAb therapy as an outpatient, it is important to have a caregiver available who is capable of monitoring you for side effects and who can take appropriate action. You will need some basic equipment at home, including a thermometer. Your medical team may also recommend a blood pressure cuff and pulse oximeter.

You will also need to have reliable transportation to and from the hospital for treatment and follow-up appointments.

Side Effects of BsAb Therapy

Common side effects may include mild, flu-like symptoms, such as fever, nausea, vomiting and diarrhea. Rarely, some people develop severe side effects. Side effects can differ depending on a person’s health and other medical conditions, their type of cancer and how they respond to treatment.

Serious Side Effects

Potential complications may include neurological toxicities, cytokine release syndrome, decreased blood cell counts or depleted immune cells.

Neurological toxicities can cause problems talking or understanding speech, balance issues, headaches, dizziness, confusion, fatigue or (rarely) seizures. These side effects are most often seen early — usually in the first weeks to months of treatment. They are treated with medications like corticosteroids.

Cytokine release syndrome (CRS) happens when T cells release too many proteins (cytokines) that stimulate the immune system. If this happens, the immune system goes into overdrive. Symptoms of CRS include low blood pressure, fever and shortness of breath.

Blood problems — decreased blood cell counts — can include a higher risk of bleeding and developing infections. Low white cell blood counts (neutropenia), low blood platelet counts (thrombocytopenia) or low red blood cell counts (anemia) may happen.

• Neutropenia may develop quickly during treatment. Since white blood cells fight infections, low white cell blood count can lead to bacterial pneumonia or other serious infections. Fever, rash, swollen lymph nodes or painful sores around the mouth or anus can happen. Treatment for these side effects may include medications like antibiotics, antifungals or antivirals to fight infection and medications to stimulate the bone marrow to produce more white blood cells.
• Thrombocytopenia or anemia symptoms may include bleeding from the nose or gums, heavy blood flow during menstruation or easy bruising. Your care team may recommend blood transfusions or stopping BsAb therapy for a time to manage these complications.

Immune cell problems called immune cell-associated neurotoxicity syndrome (ICANS) can happen during the “step-up” stage of BsAb therapy or close to the time you receive the first full dose. ICANS often happens after cytokine release syndrome.

Early ICANS symptoms can include confusion, having a hard time finding words and problems with fine motor skills like writing, typing, fastening buttons or tying shoes. Low-grade ICANS can resolve by itself with early treatment that includes supportive care and medications like corticosteroids.

Why You Should Choose to Come to the Froedtert & MCW Cancer Network for BsAb Therapy

Our dedicated teams for leukemia, lymphoma, multiple myeloma, lung cancer and melanoma are highly experienced in delivering BsAb therapy and caring for patients receiving BsAbs. Our physicians participated in many BsAb therapy clinical trials and continue to be involved in clinical research; therefore, they are knowledgeable about current developments and new treatment options.

The team includes hematologists, medical oncologists, advanced practice clinicians, clinical pharmacists, nurses and care coordinators. Other important care team members include emergency, critical care and neurology doctors and clinicians. Your medical team may consult them to treat side effects.

Having an experienced team is critical in achieving the best possible outcomes for patients:

• Selecting patients who can benefit from BsAbs therapy and who are most likely to tolerate it
• Selecting the best BsAb therapy for each patient’s unique needs
• Recognizing the symptoms of serious side effects and knowing how to manage them
• Having a team prepared to counteract serious side effects in a timely manner
• Providing patients with easy-to-understand information about BsAb therapy, so they can participate in making their treatment successful. This includes education about concerning symptoms and knowing when to alert their care team or seek emergency care.