Axicabtagene ciloleucel (Yescarta)

How is this drug name pronounced?

Axicabtagene ciloleucel: AK-see-KAB-tuh-jeen sy-loh-LOO-sel

Yescarta: yes-KAR-tuh


What cancer(s) does this drug treat?

Yescarta is approved for:

Advanced large B-cell non-Hodgkin lymphoma

Adults with large B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), whose cancer either did not respond to previous treatment (refractory) or responded to two or more previous treatments but then came back (relapsed).

Limitations of use

Age: Yescarta has not been studied in pediatric patients under the age of 18.
Fertility/Pregnancy/Breastfeeding: The effects of Yescarta on fertility are not known. Yescarta is not recommended for women who are pregnant. The risks associated with Yescarta 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

Yescarta is made from the patient’s own T cells (a type of white blood cell). In order to make Yescarta, blood is collected from the patient’s vein – this process usually takes 3 to 4 hours. 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 Yescarta from the collected blood could take approximately 3 to 4 weeks.

Illustration of how Yescarta is made


How is this drug given to the patient?

Starting 5 days before receiving Yescarta, patients are treated with a 3-day course of chemotherapy to remove white blood cells. The reduction of white blood cells in the patient gives the CAR T cells in Yescarta enough space to multiply and provides the CAR T cells with enough resources needed to persist in the patient longer. About an hour before receiving Yescarta, patients receive acetaminophen and an antihistamine to reduce the chance of reactions to the infusion.

Patients receive Yescarta through an intravenous (IV) infusion (through a tube in the vein). The administration of Yescarta usually takes about 30 minutes.

Timeline of IV infusion with Yescarta

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


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.

In a clinical trial of adult patients with relapsed or refractory large B-cell non-Hodgkin lymphoma, 58% of patients who were treated with Yescarta had complete response (no signs of cancer left), and another 25% had a partial response (the cancer shrunk but did not fully go away) two years after treatment.


What are the side effects?

Most patients receiving Yescarta experience serious side effects. Some side effects, such as cytokine release syndrome (CRS) and neurological toxicities, may be severe or life-threatening. Patients will be monitored daily by their health care provider for at least 7 days after infusion of Yescarta. Patients and caregivers receive careful instructions to monitor for signs and symptoms related to CRS and neurological toxicities. 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 Yescarta or by other immune cells in the patient’s body. Signs and symptoms of CRS include high fever, chills, difficulty breathing, fast or irregular heartbeat, severe nausea, vomiting, diarrhea, very low blood pressure, low oxygen level, and dizziness or lightheadedness. CRS typically occurs between 1 and 12 days after Yescarta 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, tremors, seizures, headache, loss of balance, and difficulty speaking and understanding. Neurological toxicities typically occur about 4 to 5 days after Yescarta infusion, but could occur 8 weeks or later after infusion.

Other side effects

Yescarta can lead to other side effects, some of which could be long-lasting. The CAR T cells in Yescarta 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 Yescarta. 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

Kite Pharma, subsidiary of Gilead Sciences

Approval

FDA and EMA

Other references


Understanding Cancer Immunotherapy Research

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