Oncology Overview: Taking a Closer Look at Axicabtagene Ciloleucel

Axicabtagene ciloleucel (Yescarta) received accelerated FDA approval on March 5, 2021, for the treatment of adult patients with relapsed or refractory FL after 2 or more lines of systemic therapy.

Axicabtagene ciloleucel (Yescarta; Kite Pharma, Inc, a Gilead Company) is a chimeric antigen receptor (CAR) T-cell therapy that is FDA-approved for 2 types of non-Hodgkin lymphoma (NHL).1,2

NHL is a cancer that starts in the white blood cells (lymphocytes), and the most common types in the United States include diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma (FL).3,4

An important milestone occurred when axicabtagene ciloleucel became the first FDA-approved CAR T-cell therapy for indolent FL, which has limited treatment options available.1,2 Indolent FL grows slowly, but it can become more aggressive over time.3 Pharmacists can play an important role in managing patients receiving axicabtagene ciloleucel therapy.

Indications

Axicabtagene ciloleucel received accelerated FDA approval on March 5, 2021, for the treatment of adult patients with relapsed or refractory FL after 2 or more lines of systemic therapy.1,2,5

The approval was based on the results from the ZUMA-5 single-arm, open-label, multicenter ongoing trial, which demonstrated that 91% of patients with relapsed or refractory FL responded to axicabtagene ciloleucel. Additionally, approximately 74% of individuals were in continued remission at 18 months.1

Axicabtagene ciloleucel is also approved for adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL resulting from FL.5

Mechanism of Action

Axicabtagene ciloleucel is a CAR T-cell immunotherapy that works by identifying and attacking target cancer cells.5

Dosage and Administration

Axicabtagene ciloleucel is administered as an intravenous (IV) infusion at a certified health care facility.5 Each single infusion bag of axicabtagene ciloleucel contains a suspension of CAR-positive T cells in approximately 68 mL. The target dose is 2 x 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 x 108 CAR-positive viable T cells.5

It is important to ensure that the patient’s identity matches the identifiers on the axicabtagene ciloleucel cassette and infusion bag.5 Patients should receive premedication with acetaminophen 650 mg orally and diphenhydramine 12.5 mg IV or orally approximately 1 hour before axicabtagene ciloleucel infusion to prevent adverse effects (AEs).5

Warnings, Precautions, and Patient Counseling Points

Axicabtagene ciloleucel carries a Boxed Warning that cytokine release syndrome (CRS) can occur in patients receiving the infusion, which can be life-threatening or fatal.5 Patients with active infections or inflammatory disorders should not receive axicabtagene ciloleucel.5

Additionally, severe or life-threatening CRS should be treated with tocilizumab monotherapy or combined with corticosteroids.5 Fatal or life-threatening neurologic toxicities are also part of the Boxed Warning for axicabtagene ciloleucel and corticosteroids can be administered to manage symptoms.5 

Patients should be monitored for at least 7 days at a certified health care facility following axicabtagene ciloleucel infusion for the signs and symptoms of CRS and neurologic toxicities.5 Pharmacists should educate patients to remain close to the facility for at least 4 weeks following infusion should any AEs occur.5

Axicabtagene ciloleucel is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS program, which includes the following requirements:5

  • Health care facilities that dispense and administer axicabtagene ciloleucel must be enrolled and comply with the REMS requirements. Certified health care facilities must have on-site, immediate access to tocilizumab, and at least 2 doses must be available for each patient within 2 hours after axicabtagene ciloleucel infusion for the treatment of CRS.
  • Certified health care facilities must ensure that health care providers who prescribe, dispense, or administer axicabtagene ciloleucel are trained about managing CRS and neurologic toxicities.

Due to the risk of neurological AEs (e.g. seizures, mental status changes), patients should be advised to avoid driving or operating heavy or dangerous machinery for 8 weeks after receiving an axicabtagene ciloleucel infusion.5 Patients should also be educated to seek emergency medical attention immediately if they experience any of the following AEs:5

  • Fever (100.4ºF or higher)
  • Difficulty breathing
  • Chills or shaking chills
  • Dizziness or lightheadedness
  • Severe nausea, vomiting, or diarrhea
  • Fast or irregular heartbeat
  • Severe fatigue or weakness
  • Confusion
  • Speech difficulties
  • Tremors
  • Seizures
  • Pregnancy and Lactation

There are no available studies evaluating axicabtagene ciloleucel use in pregnant women, so it is unknown whether the therapy can cause fetal harm.5 Based on the mechanism of action, there is the potential to cause B-cell lymphocytopenia in the developing fetus.5

Therefore, axicabtagene ciloleucel is not recommended during pregnancy according to the manufacturer.5 Data on the use of axicabtagene ciloleucel in breastfeeding are not available and it is unknown if it is present in human milk.5

References

  1. U.S. FDA approves Yescarta for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy [News release].Kite Pharma.March 5, 2021.Accessed July 17, 2021.https://www.kitepharma.com/news/press-releases/2021/3/us-fda-approves-yescarta-for-relapsed-or-refractory-follicular-lymphoma-after-two-or-more-lines-of-systemic-therapy.
  2. FDA grants accelerated approval to axicabtagene ciloleucel for relapsed or refractory follicular lymphoma [News release].FDA.March 5, 2021.Accessed July 17, 2021.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-axicabtagene-ciloleucel-relapsed-or-refractory-follicular-lymphoma.
  3. American Cancer Society.What is Non-Hodgkin lymphoma?Accessed July 17, 2021.https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/what-is-non-hodgkin-lymphoma.html.
  4. Lymphoma Research Foundation.About lymphoma.Accessed July 17, 2021.https://lymphoma.org/aboutlymphoma/nhl/.
  5. Yescarta.Prescribing information.Kite Pharma; 2021.https://www.gilead.com/-/media/files/pdfs/medicines/oncology/yescarta/yescarta-pi.pdf.Accessed July 17, 2021.