Innovative cancer treatment in the USA: CAR T-cell therapy at Cleveland Clinic, Ohio

04 July
Diagnosis & Treatment
2336

Last year, the FDA approved another innovative cancer treatment in the USA called CAR T-cell therapy (CART).

This therapy is now available only in the best cancer centers of the world including Cleveland Clinic.

CAR (Chimeric antigen receptor) T-cell therapy is a new type of adoptive immunotherapy.

This promising approach uses a patient's own modified effector immune cells (T-lymphocytes) to seek specific surface antigens and destroy tumors throughout the body.

Adoptive immunotherapy indications:

1. Aggressive B-cell lymphoma
2. Large B-cell lymphoma, including DLBCL
3. Acute lymphoblastic leukemia in children and adults
4. Other tumors undergoing clinical trials

Previously this unique method was limited to small trials. Despite the high cost and technical complexity, CAR T-cell technology captured the attention of oncologists with its outstanding clinical results in advanced stages of blood cancer.

Now we have highly specific killer cells that are virtually harmless to healthy tissues. They recognize tumor antigens or antigen combinations. They are only activated in a certain environment (for example in the hypoxic microenvironment). They easily overcome the protective mechanisms of tumor cells and resistance to standard therapy.

CAR T-cell therapy at Cleveland Clinic:

1. Yescarta. Used to treat diffuse form of lymphoma DLBCL in adults if other methods are ineffective or the disease has returned soon after therapy.
2. Kymriah. Indicated for children and young adults with advanced ALL.

Before treatment, it is necessary to undergo examination. If the patient is suitable for CAR T-cell therapy, the whole process will take several weeks. Some stages require staying in hospital.

CAR T-cell therapy: how does it work?

This is a personalized cell-based method that uses some patient's lymphocytes. Before the infusion, your doctor collects blood specimen, which is treated in the lab. The resulting T cells express chimeric antigen receptors (CAR) to recognize tumor antigens and destroy cancer.

CAR T-lymphocyte can be used against numerous tumor antigens. All these antigen molecules are recognized by small adaptive molecules. This is truly a universal weapon for oncology.

Chimeric antigen receptors react not only to simple proteins, but also to other molecules (sugars, glycoprotein and glycosphingolipid). This feature significantly expands the spectrum of action and increases the effectiveness of immunotherapy.

Results of CAR T-cell cancer treatment in the USA

Over the past decades, surgical resection of the tumor, highly toxic chemotherapy and radiation therapy remained leading methods of cancer treatment in the USA. Standard biological agents like trastuzumab (Herzeptin) personified the success of American immunotherapy. Old options are replaced by so called adoptive cell transfer, which involves the collection and modification of the patient's own T-lymphocytes to attack a specific tumor cells. Among modern methods of adoptive immunotherapy (TIL, TCR, CAR) the most promising is CART.

FDA experts approved the use of this method for the treatment of acute lymphoblastic leukemia in children, as well as in adults with advanced stages of lymphoma. There are some promising results on advanced solid tumors including bowel and breast cancer.

4 out of 5 patients with advanced lymphoma receiving Yescarta demonstrated response to therapy. This means that the vast majority of people will benefit from treatment. According to other studies, 4 out of 5 patients with ALL receiving Kymriah achieved remission.

Potential side effects of treatment

As a rule, side effects occur in the first few hours or days after the introduction of modified T-lymphocytes. These effects associated with the activation of the immune system.

- Neurotoxicity: encephalopathy symptoms including confusion, thinking and memory problems, aphasia, seizures, loss of balance and coordination, tremor.
- Cytokine release syndrome, CRS: influenza-like symptoms, dyspnea, hypotension, tachycardia, low blood oxygenation, nausea and diarrhea.
- Low blood counts: anemia, neutropenia.

Described side effects are usually short-term and completely reversible, although the long-term side effects of CART are currently being studied. Ask your oncologist about potential risks.

Cleveland Clinic CAR T-Cell Therapy Program

Being one of the best US cancer centers, Cleveland Clinic attracts thousands of foreign patients annually from all over the world. Experts of the team Global Patient Services, providing access to the most advanced technologies for cancer diagnosis and treatment including CART. This program is suitable for patients with appropriate diagnoses who previously received standard chemotherapy. You need to undergo an evaluation. Oncologists will examine the medical history and previous treatment, selecting the optimal therapeutic options for your case.

You need to take all medical records translated into English, the biopsy results (if available) and the latest images (MRI).

We recommend to come along with a friend or relative who will support you and help to conduct a dialogue.

Also prepare a list of questions for your oncologist.

You will have to stay in Cleveland for a couple of days until the results of lab tests are ready. If CAR T-cell therapy is appropriate for your case, doctor will develop a personal treatment plan. The wait time depends on different factors, including health condition and laboratory capacity.

What to expect during CART?

Although it is largely experimental and innovative cancer treatment in the USA, the leading hospitals have worked out the optimal regimens of CART. These regimens are safe and reliable.

The first stage: leukopheresis

First, the doctor takes a small amount of patients own blood with a special device. The collected biomaterial is then separated to produce purified leukocytes – this is called leukopheresis. Then the remaining blood is returned to the patient's body by the machine.

This stage takes several hours (usually up to 5 hrs).

The second stage: processing of T-lymphocytes

After collection of the biomaterial, the obtained T-lymphocytes are delivered to the laboratory for subsequent genetic modification and activation. Specially trained doctors induce the expression of chimeric antigen receptors (CAR) necessary to find and destroy tumor cells.

At this stage, the patient usually goes home.

The third stage: chemotherapy prior to CART

When CAR T-lymphocytes are ready, patient has to prepare for the introduction of cells. Additional tests before the infusion are mandatory: even at this point it may become clear that CART is no longer an option. Then doctor will prescribe chemotherapy.

You may need continuous monitoring before infusion.

The fourth stage: T-cell infusion

When chemotherapy is complete, it`s time to return the activated cells to the patient's bloodstream. Infusion usually lasts 30-90 minutes. Preparatory procedures and monitoring after infusion takes up to 5-6 hours. The doctor will leave you in the hospital for a few days to monitor serious side effects.

What to expect after returning home?

First weeks after discharge, your caregivers should stay with you 24/7.

Adverse events usually occur in the first hours or days after the infusion. But even after returning home, you should carefully monitor your condition and follow the doctor's recommendations.

Plan to visit your oncologist at Cleveland Clinic for monitoring over the next year.

According to the requirements of the FDA, patients after CART should be observed up to 15 years.