Kymriah (tisagenlecleucel) is an approved CAR T-cell therapy marketed by Novartis to treat children and young adults with refractory or relapsing acute lymphoblastic leukemia (ALL).

Refractory means that previous treatments have not achieved remission — that is, been able to rid the body of cancer cells — and relapsing means the cancer has returned after initial remission was achieved.

Novartis developed Kymriah in collaboration with the University of Pennsylvania under the experimental name CTL019.

How Kymriah works

CAR T-cell therapy differs from other biologic cancer treatments because it is created from the patient’s own T-cells, a type of white blood cell that coordinates the immune response to identify and destroy invaders. The T-cells are first harvested from the patient’s blood, then genetically engineered to produce proteins on the cell’s surface called chimeric antigen receptors, or CARs. The modified cells are called CAR T-cells.

The CAR enables the modified T-cells to identify and bind to a specific protein on the surface of tumor cells.  In the case of Kymriah, the T-cells are modified to bind to the CD19 receptor on the surface of B-cells, another type of white blood cell.

Once the modified T-cells have been created, they are infused into the patient’s bloodstream. The CAR also plays a role in helping these cells multiply inside the body and survive in circulation,  creating a growing army of CAR T-cells to identify and destroy the cancerous B-cells in patients with ALL.

Kymriah in clinical trials

In August 2017, the U.S. Food and Drug Administration approved Kymriah for use in children and young adults up to age 25 with B-cell ALL that had not responded well to earlier treatment.  The decision followed a unanimous recommendation for approval by the oncologic drugs advisory committee, which oversees cancer treatments for the FDA.

Kymriah is the first CAR T-cell therapy to be approved by the FDA. The approval was based on three key clinical trials, two considered supportive and one pivotal.

The first supportive study was a single-center Phase 1/2a trial (NCT01626495) sponsored by the University of Pennsylvania and carried out at the Children’s Hospital of Philadelphia. In this trial, published in the New England Journal of Medicine in October 2014, 27 of the 30 patients treated with Kymriah achieved complete remission, with 67 percent still in remission after six months. Some of these patients had had stem cell transplants that had not worked.

The second supporting study is a Phase 2 single-arm, open-label study (NCT02228096) assessing the safety and effectiveness of Kymriah in children with ALL. It began in 2014 and is still recruiting participants at multiple sites across the United States. It is expected to be completed by October 2024.

The pivotal study (NCT02435849), called ELIANA, is a Phase 2 multinational clinical trial with sites in the United States, Canada, Japan, Europe, and Australia. In this study, 68 children and young adults with relapsing or refractory B-cell ALL received a single infusion of Kymriah. The results so far are an 83 percent overall remission rate within the first three months of infusion, with 75 percent remaining cancer-free six months after remission. The trial is still recruiting participants.

Additional information

Patients treated with CAR T-cell therapies often experience cytokine release syndrome (CRS), an inflammatory reaction related to the release of the signaling proteins that recruit immune cells. In most cases, CRS is mild and consists only of flu-like symptoms, but the reaction can also be severe or even life-threatening. In the clinical trials, CRS did occur, but was largely treatable and more common in those who had a more severe disease to begin with.


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