Yescarta (Axicabtagene Ciloleucel): A Groundbreaking CAR-T Therapy for Lymphoma
Yescarta (Axicabtagene Ciloleucel): A Groundbreaking CAR-T Therapy for Lymphoma
Yescarta, also known as axicabtagene ciloleucel, is a revolutionary chimeric antigen receptor T-cell (CAR-T) therapy that has been hailed as a significant breakthrough in the treatment of certain types of lymphoma. Developed by Kite Pharma, a subsidiary of Gilead Sciences, this cutting-edge therapy harnesses the power of the body’s own immune system to fight cancer cells.
Approval and Indications
Yescarta received its initial approval from the U.S. Food and Drug Administration (FDA) on October 18, 2017, for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) after two or more lines of systemic therapy. Subsequently, in April 2021, the FDA expanded Yescarta’s indications to include the treatment of relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.
Mechanism of Action
CAR-T cell therapy is a form of immunotherapy that involves genetically modifying a patient’s own T-cells (a type of immune cell) to recognize and attack cancer cells. In the case of Yescarta, the T-cells are engineered to express a chimeric antigen receptor (CAR) that targets the CD19 protein, which is present on the surface of B-cell lymphoma cells.
The process begins with collecting the patient’s T-cells through apheresis, a procedure similar to donating blood. These T-cells are then genetically modified in a laboratory to express the CAR specific to CD19. The modified cells, now known as Yescarta, are then infused back into the patient’s body, where they can seek out and destroy the cancerous B-cells.
Clinical Trials and Efficacy
Yescarta’s efficacy has been demonstrated through several clinical trials, including the pivotal ZUMA-7 phase 3 trial for R/R LBCL and the ZUMA-1 phase 2 trial.
ZUMA-7 Trial:
– The global, randomized, multicenter phase 3 ZUMA-7 trial compared Yescarta to standard second-line therapy in 359 patients with R/R LBCL.
– Results showed an overall response rate (ORR) of 83% with Yescarta, compared to 50% with standard therapy.
– The complete response rate (CR) was 65% with Yescarta, significantly higher than the 32% achieved with standard therapy.
ZUMA-1 Trial:
– The phase 2 ZUMA-1 trial evaluated Yescarta in patients with R/R LBCL and follicular lymphoma.
– At the 5-year follow-up, the overall survival rate for patients with R/R LBCL was 42.6%.
– Notably, 92% of surviving patients at 5 years did not require additional cancer treatment, suggesting the possibility of a cure.
Safety and Side Effects
Like many cancer treatments, Yescarta can cause side effects, some of which can be severe. The most common side effects include cytokine release syndrome (CRS), neurological toxicities, and infections.
Cytokine Release Syndrome (CRS):
– CRS is a systemic inflammatory response that can occur when the CAR-T cells become activated and release high levels of cytokines.
– Symptoms of CRS can range from mild to life-threatening and may include fever, nausea, chills, headache, and low blood pressure.
– In the ZUMA-7 trial, the incidence of CRS was 92%, with 7% of patients experiencing severe (grade ≥3) CRS.
Neurological Toxicities:
– CAR-T cell therapy can also cause neurological toxicities, such as confusion, tremors, and seizures.
– In the ZUMA-7 trial, 74% of patients experienced neurological toxicities, with 25% experiencing severe (grade ≥3) events.
Infections:
– Patients receiving Yescarta are at an increased risk of developing infections due to the immunosuppressive nature of the treatment.
– Frequent monitoring and prompt treatment of infections are crucial for patient safety.
Patient Selection and Monitoring
Careful patient selection and close monitoring are essential for the safe and effective use of Yescarta. Patients must meet specific eligibility criteria, and their overall health and potential risk factors must be carefully evaluated before treatment.
Ongoing monitoring for side effects, such as CRS and neurological toxicities, is crucial during and after Yescarta infusion. Healthcare professionals must be prepared to manage these side effects promptly and effectively, using established protocols and supportive care measures.
FAQs
What is Yescarta used to treat?
Yescarta (axicabtagene ciloleucel) is used to treat relapsed or refractory large B-cell lymphoma (R/R LBCL) and relapsed or refractory follicular lymphoma (FL).
How does Yescarta work?
Yescarta is a CAR-T cell therapy that targets CD19, a protein expressed on the surface of B-cells. The therapy involves modifying a patient’s T-cells to express a chimeric antigen receptor (CAR) that recognizes and destroys cancerous B-cells.
What are the side effects of Yescarta?
The most significant side effects of Yescone include cytokine release syndrome (CRS) and neurotoxicity. CRS is a systemic inflammatory response that can lead to fever, hypotension, and organ dysfunction. Neurotoxicity can manifest as confusion, seizures, and other neurological symptoms.
How long does it take to prepare for Yescarta treatment?
The preparation for Yescarta treatment typically involves several steps, including initial assessments, blood tests, imaging studies, and apheresis to collect T-cells. The entire process can take several weeks, depending on the individual patient’s needs and the availability of manufacturing facilities.
Is Yescarta covered by insurance?
Insurance coverage for Yescarta varies depending on the patient’s insurance plan and the specific indications for treatment. Many insurance companies cover Yescarta for eligible patients, and patient assistance programs may also help to reduce the financial burden.
What is the long-term outlook for patients treated with Yescarta?
The long-term outlook for patients treated with Yescarta is promising, with a 5-year overall survival rate of 42.6% in the ZUMA-1 trial. Many patients who survive for five years do not require additional cancer treatment, indicating a high likelihood of long-term remission or even cure.
How can I find a provider for Yescarta treatment?
To find a provider for Yescarta treatment, patients should consult with a medical oncologist who specializes in CAR-T therapy. These experts can provide detailed information about the treatment process, potential side effects, and long-term outcomes.
What is the future of CAR-T therapy?
The future of CAR-T therapy is bright, with ongoing research exploring new targets, reducing side effects, and improving accessibility. Advances in manufacturing processes and the development of “off-the-shelf” CAR-T therapies may make this treatment more affordable and accessible for a broader range of patients.
By addressing these frequently asked questions, we hope to provide a comprehensive understanding of Yescarta and its role in the treatment of lymphoma. For more information or to discuss treatment options, patients should consult with a medical oncologist who specializes in CAR-T therapy.