Tisagenlecleucel (Kymriah)

How is this drug name pronounced?

Tisagenlecleucel: TIH-suh-jen-LEK-loo-sel

Kymriah: kim-RY-uh


What cancer(s) does this drug treat?

Kymriah is approved for:

Advanced B-cell acute lymphoblastic leukemia (ALL)

Children and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) whose cancer did not respond to previous treatment (refractory disease), or responded to two or more previous treatments but then came back (relapsed disease).

Advanced diffuse large B-cell lymphoma (DLBCL)

Adults with diffuse large B-cell lymphoma (DLBCL) whose cancer came back or did not respond (relapsed or refractory, respectively) after two or more previous treatments.

Limitations of use:

Age: Kymriah has not been studied in patients under the age of 3. The safety and efficacy of Kymriah in patients over 65 years of age have not been established.
Exclusions: Currently, Kymriah is not manufactured for patients who test positive for active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
Fertility/Pregnancy/Breastfeeding: The effects of Kymriah on female and male fertility are not known. Kymriah is not recommended for women who are pregnant. The risks associated with Kymriah during breastfeeding are not known, and risk to a breastfed infant cannot be excluded.


What type of immunotherapy is this?

T Cell Therapy

  • CAR T cell therapy

How does this drug work?

  • Target: CD19

Kymriah is made from the patient’s own T cells (a type of white blood cell). In order to make Kymriah, blood is collected from the patient’s vein – this process usually takes 3 to 6 hours and may need to be repeated. In a process called leukapheresis, the white blood cells (including T cells) are separated from the collected blood, and the rest of the blood is returned to the patient. The collected white blood cells are sent to a specialized manufacturing facility where the patient’s T cells are genetically modified in such a way that they make a protein on their surface called chimeric antigen receptor (CAR). The modified T cells (“CAR T cells”) are multiplied to create millions of CAR T cells.

The CAR on the surface of the modified T cell can attach to a protein called CD19 on the surface of the cancer cell. When CAR attaches to CD19, T cells recognize the cancer cells and kill them. The entire process to create Kymriah from the collected blood could take approximately 3 to 4 weeks.

Detailed illustration on how Kymirah is made


How is this drug given to the patient?

Two to 14 days before receiving Kymriah patients are usually treated with a short course of chemotherapy to reduce the number of white blood cells. The reduction of white blood cells in the patient gives the CAR T cells in Kymriah enough space to multiply and provides the CAR T cells with enough resources needed to persist in the patient longer. About 30 to 60 minutes before receiving Kymriah, patients receive acetaminophen and an antihistamine to reduce the chance of reactions to the infusion.

Patients receive Kymriah through an intravenous (IV) infusion (through a tube in the vein). The administration of Kymriah usually takes about an hour.

Timeline illustration of the Kymirah process

Patients should plan to stay close to the treatment location for at least 4 weeks after receiving Kymriah.


What are the observed clinical results?

It is important to keep in mind that each patient’s actual outcome is individual and may be different from the results found in the clinical studies. In addition, with immunotherapy, sometimes it takes several months for responses to be observed. The long-term clinical trial data currently available is limited, and more clinical trials are ongoing.

B-cell ALL

In several clinical studies leading up to the approval of Kymriah, about 81-83% of patients with B-cell ALL who were infused with Kymriah had a complete response (no signs of cancer left) within 3 months of treatment. Twelve months after treatment, the likelihood of survival was 76% among all treated patients.

DLBCL

In another clinical trial, about 40% of patients with DLBCL who were infused with Kymriah had a complete response (no signs of cancer left), and another 12% had a partial response (the cancer shrunk but did not fully go away) within 14 months of treatment. Twelve months after treatment, the likelihood of survival was 49% among all treated patients and 90% among patients with a complete response.


What are the side effects?

Most patients receiving Kymriah experience serious side effects. Some side effects, such as cytokine release syndrome (CRS) and neurological toxicities, may be severe or life-threatening. Patients and caregivers receive careful instructions to monitor for signs and symptoms related to CRS and neurological toxicities, and both conditions are managed by the health care provider.

Cytokine release syndrome (CRS)

CRS is caused by a widespread release of molecules called cytokines, which are involved in inflammation and can affect the function of various organs. Cytokines may be released by the CAR T cells in Kymriah or by other immune cells in the patient’s body. Symptoms of CRS include high fever, chills, difficulty breathing, severe muscle or joint pain, severe nausea, vomiting, diarrhea, very low blood pressure, and dizziness or lightheadedness. CRS typically occurs between 1 and 10 days after Kymriah infusion, and the health care provider should be immediately notified if symptoms occur.

Neurological toxicities

Some of the cytokines released during CRS can result in disruption of the blood-brain barrier, leading to the development of neurological toxicities. Symptoms of neurological toxicities include confusion, altered or decreased consciousness, seizures, loss of balance, and difficulty speaking and understanding. Neurological toxicities typically occur about 7 days after Kymriah infusion, but could occur 8 weeks or later after infusion.

Other side effects

Kymriah can lead to other side effects, some of which could be long-lasting. The CAR T cells in Kymriah kill cancer cells that have the molecule CD19 on their surface; however, CD19 is also found on the surface of healthy B cells, which can also be killed by Kymriah. The decrease in healthy B cells leads to low levels of antibodies (immunoglobulins) and an increased risk of serious infections. Other possible side effects include low blood cell counts, serious allergic reactions, and development of other cancers. For a more complete list of possible side effects, see the full prescribing information.


Additional information

Manufacturer

Novartis

Approval

FDA and EMA

Other references


Understanding Cancer Immunotherapy Research

Search