Side effects of immunotherapy

Immunotherapy generally causes fewer side effects than other cancer treatments because it only targets your immune system, and not all the cells in your body. The side effects that you experience depend largely upon the type of cancer you have, the specific immunotherapy drug, the dose you receive, and how healthy you are when you begin treatment. At Sheba, we aim to keep the side effects to a minimum, and we encourage our patients to inform us about any bothersome symptoms – so we can help to alleviate them.

Types of cancer immunotherapy

Experiments with many newer types of immunotherapy are ongoing, and Sheba Medical Center is committed to staying up-to-date with the newest treatments.

The types of immunotherapy that are used to help the immune system combat cancer directly include:

Monoclonal antibodies

These are man-made versions of antibodies (immune system proteins) that are custom-designed to attach to specific targets, called antigens, found on cancer cells. These monoclonal antibodies work to mark the cancer cells so the immune system can identify them better.

Checkpoint inhibitors

These drugs boost the power of the immune system so that it can respond more effectively to a tumor.

Adoptive cell transfer

These treatments strengthen the natural ability of your white blood cells to subdue cancer. To perform this type of immunotherapy, your active T-cells are extracted, modified, and/or grown in a laboratory, and then injected back into your body. CAR T-cell therapy and TIL therapy are particular types of adoptive cell transfer.

Cancer vaccines

These substances are administered to people either as a way to treat existing cancers by optimizing the body’s immune system against specific cancer or to prevent cancer from developing. When used as a treatment vaccine, these immunotherapy drugs are often combined with other types of therapies. Provenge is an example of a customized cancer treatment vaccine that triggers an immune response against metastatic prostate cancer. Tests are being conducted on a variety of experimental treatment vaccines for other types of cancers, such as brain tumors, melanoma, breast cancer, leukemia, kidney cancer, and others.

The types of immunotherapy that are used to improve the body’s general immune response to fighting cancer:

Cytokines

The purpose of this type of immunotherapy is to manipulate the immune response in such a way as to generate the appropriate immune effector cells to eradicate tumors. It involves injecting artificial cytokines, proteins our body produces that assist in the body’s normal immune responses to cancer. Two examples of cytokines that may be used to fight cancer are interleukins and interferon.

BCG

This type of immunotherapy involves the use of a weakened form of the bacteria that causes tuberculosis in order to treat bladder cancer. The injection of BCG (Bacillus Calmette-Guerin) into the bladder leads to an immune response against the cancer cells.

Depending on the form of immunotherapy being administered, it can be given intravenously, as an oral medication, as a topical cream, or intravesically (directly into the bladder).

Diseases Treated by CAR T-Cell Therapy

At Sheba, we offer therapy for the following types of cancer:

• Acute Lymphocytic Leukemia (ALL), Adult
• Non-Hodgkin Lymphoma (NHL), Adult and Child
• Leukemia (ALL), Child
• Multiple Myeloma
• Acute Myelogenous Leukemia (AML)

How is CAR T-Cell Therapy Given?

Your medical team at Sheba will design your customized CAR T-cell therapy to target your specific type of cancer. We are committed to clear and open communication with every patient, so there is no confusion and you always know what to expect. The following outline is a step-by-step explanation of how CAR T-cell therapy is given.

1. Testing for Candidacy: We will perform various tests and screenings to evaluate whether CAR T-cell therapy is a suitable treatment for you.
2. T-Cell Collection: By using a special machine for apheresis, T cells will be separated from the rest of your blood cells.
3. Cell Engineering: Your T-cells will be sent to a lab where they are genetically modified to produce CARs on their surface. CARs are proteins that enable the T-cells to identify particular antigens on the surface of tumor cells.
4. Growing T-cells: The specially altered T-cells are grown in our on-site Sheba laboratory until there are millions of them; this process can take a few weeks.
5. Chemotherapy: Before we infuse the CAR T-cells into your body, we may give you chemotherapy treatments to kill additional cancer cells, which creates more space for the CAR T-cells to proliferate in your body.
6. Infusing T-cells: Shortly after chemo, you will be hospitalized so that we can re-infuse the CAR T-cells into your body. This process is performed in a similar manner to a blood transfusion.
7. Recovery: While you will only receive a one-time infusion, you may need to stay in the hospital for a few weeks so our doctors can monitor your condition closely and manage any side effects, as needed. Typically, it takes about two to three months to recover.
8. Follow-up: Your Sheba doctors will instruct you about how frequently you must return over the next few months for periodic follow-up appointments. We will evaluate your overall health thoroughly, checking your body’s response to the therapy. Over the next several years, you will return for blood tests, physical examinations, and/or bone marrow biopsies and PET or CT scans.

Patient Testimonial – After CAR T-Cell Therapy

“Like a bolt from the blue…” That was Sam Turel’s reaction when first diagnosed with chronic lymphoproliferative disease. Sam had enjoyed an active full life, but when he heard the words “blood cancer,” he fell into acute despair. After years of initial treatments slowed him down, he was later diagnosed with chronic lymphocytic leukemia (CLL). It was time to seek an advanced treatment method, and Sam chose Sheba for CAR-T cell therapy.

Read Sam’s story and the role CAR-T therapy played in it.

Diseases Treated by Stem Cell / Bone Marrow Transplantation

At Sheba, we offer stem cell transplantation for the following types of cancer:

• Acute Lymphocytic Leukemia (ALL), Adult and Child
• Acute Myeloid Leukemia (AML), Adult and Child
• Chronic Lymphocytic Leukemia (CLL), Adult and Child
• Chronic Myelogenous Leukemia (CML), Adult and Child
• Non-Hodgkin Lymphoma (NHL), Adult and Child
• Hodgkin Lymphoma, Adult and Child
• Multiple myeloma, Adult
• Myelofibrosis, Adult
• Osteosarcoma, Child
• Neuroblastoma, Child
• Ewing’s sarcoma or Ewing sarcoma, Child
• Wilms’ tumor (Nephroblastoma), Child
• Medulloblastoma, Child
• Rhabdomyosarcoma, Child

Side effects during conditioning

Conditioning treatments get your body ready for a stem cell transplant, and they may involve chemotherapy and/or radiation therapy. Side effects may include:

• Nausea, vomiting
• Diarrhea
• Mouth sores
• Fatigue
• Dry mouth
• Rashes
• Hair loss
• Difficulty breathing

Side effects during stem cell infusion

As you receive your new stem cells, the most common symptoms include:

• Headaches
• Fever
• Chills
• Nausea
• Flushing

These side effects can present up to one hour after the infusion is completed.

Side effects during engraftment

Engraftment is the phase that follows the infusion of new stem cells. This is when the transplanted stem cells start to produce new blood components in your body, such as platelets and red blood cells. Typical side effects during engraftment include:

• Trouble sleeping
• Nausea
• Skin rashes
• Mucositis (causes difficulty with eating and drinking)
• Lack of appetite
• Diarrhea
• Fatigue

Post-transplant side effects

After transplantation is complete, you may experience:

• Nausea, vomiting
• Diarrhea
• Fatigue
• Lack of appetite
• Hair loss
• Skin rash
• Decreased libido
• Inflammation
• Weight changes

With time and as your immune system recovers, these side effects will usually subside.

Types of Stem Cell / Bone Marrow Transplantation

There are two main types of stem cell transplants, categorized by the source of the donor marrow: autologous transplants and allogeneic transplants.

Autologous transplants

Autologous transplants are taken from your own stem cells, typically sourced from peripheral blood that is frozen and preserved. Your stem cells must be harvested from your blood before you receive any cancer-killing treatments.

The advantage of autologous transplants is that you do not need to worry about graft-versus-host disease, which refers to when the engrafted cells attack your body.

Allogeneic transplants

Allogeneic transplants are performed using donor tissue from someone who is genetically suitable, often a close family member. The stem cells may be sourced from peripheral blood, bone marrow, or cord blood. When a perfect genetic match cannot be located, a mismatched allogeneic transplant may also be performed. In this case, the stem cells are sourced from peripheral blood and must undergo a refinement process to compensate for the riskier mismatch.

A possible advantage of allogeneic transplants is that the donor stem cells create their own immune cells, which may help to kill cancer kills that remain in your body after treatment. However, graft-versus-host disease is a risk when performing allogeneic transplants.

Patient Testimonial – After Bone Marrow Transplantation

Yulia Egorova’s young son, Ivan, was diagnosed with leukemia in Russia and needed a bone marrow transplant. After extensive research to locate the best medical facility for this advanced procedure, Yulia decided on the Bone Marrow Transplant Clinic at Sheba Medical Center. Ivan underwent a bone marrow transplant at Sheba, and the donor cells survived. He recently returned to school and lives life just like other kids.
Read Ivan’s story here

Side Effects of Radiation Therapy

Radiation therapy can lead to a variety of side effects that vary widely from person to person. The side effects that you may experience depend on the type of radiation, the dose, and which part of your body is being treated (where the radiation is aimed). Your overall health condition is also significant. Sometimes the side effects are mild and limited, while other times there are many side effects and they are severe. There is no reliable way to predict how radiation will affect each individual.

In general, there are two categories of side effects from radiation therapy: early and late. Usually, early side effects appear immediately and are short-lived. Late side effects may only appear much later on, and they can be permanent.

How is Radiation Therapy Administered?

At Sheba, we plan radiation therapy very carefully to help ensure the best results. Planning is an important part of the whole treatment process.
First, it is important to note that before radiation can be administered, the patient undergoes a simulation.
The simulation is then tested on a mannequin.
Only after these stages are completed is the patient scheduled to undergo radiation therapy.

1. During the first phase of radiation therapy, we will instruct the patient precisely about what position to lie in. It is necessary that this same position is maintained throughout each session of the treatment, so that the irradiated area remains constant. On the first visit, the parameters of the irradiated area will be determined with the aid of a simulation; sometimes, a CT scanner will be used for this purpose.
2. When treating the head and neck area, a special plastic mask helps to match the radiation exactly. The mask is fixed to the couch during the session and maintains the precise head position. The irradiated area is marked and recorded on the mask. If the radiation treatment is administered without a mask, the radiation technician will mark the skin to indicate the exact position. These marks must remain on the skin throughout the entire span of treatment.
3. We will provide the patient with detailed instructions on how to take care of the skin in the irradiated area.
4. Before each radiation session, the technician will ensure that the patient is positioned comfortably on the couch. During the treatment, which lasts only a few minutes, the patient will be left alone in the treatment room. The radiation technician will watch the patient via a monitor in an adjacent room.
5. Radiation therapy is painless, yet requires lying still for a few minutes

The above process describes the external radiation method of administering radiotherapy. In addition to external radiation, there are two other ways to administer radiotherapy:

• Internal radiation: Also called brachytherapy, this type of radiation involves implanting a sealed radioactive source inside or near the tumor. This can be done with either a temporary or permanent implant, depending on your type of cancer. Internal radiation enables a higher dose of radiation in a small area, while causing very little harm to nearby healthy cells.
• Systemic radiation: Radioactive drugs (radiopharmaceuticals) may be taken orally or injected intravenously to treat particular types of cancer, such as thyroid, prostate, and bone. These drugs travel throughout your bloodstream, and an attached antibody makes them bind to the cancer cells. There, they emit radiation and kill the cancer cells. You may need to be hospitalized while receiving this type of radiation therapy.

Diseases Treated by Targeted Therapy

Side Effects of Targeted Therapy

Targeted therapies can cause a range of side effects, although not every patient gets every side effect and some people do not experience any at all. The severity of these side effects varies widely, depending on the specific drug and the individual. Although many of the side effects can be very uncomfortable, it is essential to remember that the less extreme ones should be measured against the need to fight your cancer.

Prior to your treatment, your medical team at Sheba will inform you about the specific targeted therapy drugs that you will be given and the possible side effects. We will also monitor you closely throughout your entire course of treatment. It is important that you inform our doctors about any side effects or changes in how you feel, so we can treat any problems and help to mitigate any discomfort.

Many of the same side effects that are seen with standard chemotherapy drugs are also associated with some targeted therapy drugs, such as nausea, vomiting, diarrhea or constipation, mouth sores, headache, fatigue, shortness of breath, hair loss, and increased risk of certain infections.

Other side effects of targeted therapies may include:

Skin Problems

Targeted therapies attack the same blood vessels and growth factors that your body needs to maintain healthy skin. Prior to starting treatment, you are advised to switch to gentle, chemical- and fragrance-free soaps and shampoos. It is typical to experience:

• Rashes that itch or burn
• Sensation of a bad sunburn (even if nothing is noticeable)
• Extreme sensitivity to sunlight
• Very dry skin that may crack open
• Painful sores on your fingernails and toenails
• Sores on your scalp; hair loss or changes in hair color
• Red and swollen eyelids

High Blood Pressure

Your Sheba medical team will keep close watch on your blood pressure if you are taking one of the targeted therapy drugs, such as angiogenesis inhibitors, which can raise blood pressure. Sometimes it is necessary to take medication to lower blood pressure to safe levels.

Bleeding or Problems with Blood Clotting

Certain types of target therapy drugs interfere with the growth of new blood vessels, which can lead to problems with bleeding and bruising. If internal bleeding occurs, such as from the stomach or intestines, it can be life-threatening. If you vomit blood or dark matter (resembling coffee grounds), or see black stools or bright red blood in your stools, notify your doctor immediately.

Some types of drugs can also cause blood clots in your legs and lungs, as well as lead to a heart attack or stroke. If you suffer chest pain or sudden shortness of breath, have pain in the arm or leg, or experience a seizure – seek emergency medical care.

Slow Healing of Wounds

Targeted therapy drugs may interfere with the healing of wounds. They can also lead to perforations (holes) opening up in the intestine or stomach, which causes pain or vomiting.

Autoimmune Reactions

In some people, targeted therapies trigger the immune system to attack healthy parts of the body. This is relatively uncommon, but can be very serious.

Swelling

Inflammation around the eyes and in the face may occur. Sometimes swelling in the feet, legs, and hands also happens. Treatment isn’t always necessary, but a diuretic may be prescribed in extreme cases.

How Do Targeted Therapy Drugs Work?

Cancer cells have many changes in their DNA (genes) that makes them distinct from healthy cells. For example, these changes might cause the cell to grow or divide more rapidly than normal. However, there are many different kinds of cancer, and the gene changes in each type can be different. Targeted therapy drugs focus on some of these changes and aim to attack them. Sheba’s doctors will analyze your test results to determine which type of targeted therapy will achieve the most effective potential outcome.

There are two primary categories of targeted therapies, small molecule medicines and monoclonal antibodies. Small molecule drugs are minute enough to enter the cancer cells directly and destroy them from within. Monoclonal antibodies, which are larger, work from the outside. They attack targets on the external surface of the cells or surrounding them.

Different targeted drugs function in different ways, such as:

• Signal transduction inhibitors, the most common targeted drugs, block the signals that instruct cancer cells to rapidly divide.
• Gene expression modulators function to change the proteins that regulate how the genes in cancer cells get carried out abnormally
• Immunotherapies utilize your natural immune system to destroy cancer cells, either by boosting the immune system so it is more effective or by marking cancer cells so they are more easily identified
• Hormone therapies stop your body from producing the hormones that some cancers, such as breast and prostate, need to grow
• Angiogenesis inhibitors block the creation of new blood vessels that feed the cancer cells; these drugs can cut off blood supply to a tumor
• Apoptosis inducers cause cancer cells to follow the normal process of dying when they are old or damaged (cancer cells can often bypass this natural process)