Iovance lifileucel, marketed as Amtagvi, represents a personalized form of cell therapy for treating cancer. It is a type of immunotherapy specifically designed for each individual.
Lifileucel is the first therapy of its kind, using what are known as tumor-infiltrating lymphocytes, or TILs, to receive approval from the Food and Drug Administration (FDA) for treating a solid tumor. This approach differs from other immunotherapies by using cells that have already demonstrated an ability to target the patient’s specific cancer.
The Science of TIL Therapy
Tumor-infiltrating lymphocytes are specialized white blood cells, specifically T-cells, that have naturally left the bloodstream to enter and attack a tumor. These cells are part of the body’s intrinsic response to cancer. However, inside the tumor environment, these cells often become exhausted or are present in insufficient numbers to overcome the cancer’s defenses.
The core principle of lifileucel is to augment this natural process by isolating these TILs and multiplying them in a laboratory. This process selects for the most active cancer-fighting cells. These reinvigorated lymphocytes are then infused back into the patient to create a powerful therapeutic army.
Approved Uses and Patient Candidacy
The FDA has approved lifileucel for a specific group of adult patients diagnosed with advanced melanoma. The approval covers melanoma that is either unresectable, meaning it cannot be surgically removed, or metastatic, indicating it has spread to other parts of the body. This therapy is intended for patients whose cancer has progressed despite previous treatments.
Eligibility for lifileucel is clearly defined. A patient must have previously received treatment with a PD-1 blocking antibody, a common type of immunotherapy. If a patient’s melanoma has a specific genetic marker known as a BRAF V600 mutation, they must have also been treated with a BRAF inhibitor, sometimes in combination with a MEK inhibitor.
The treatment is not a first-line therapy but is reserved for those who have not responded to or have relapsed after these other treatments. Clinical trial data has shown that this therapy can produce lasting responses in this heavily pre-treated patient population. The median overall survival in the key clinical trial was 13.9 months, with a five-year survival rate of nearly 20%.
The Lifileucel Treatment Process
The treatment journey with lifileucel is a multi-step process that occurs over several weeks. It begins with a surgical procedure to remove a portion of the patient’s melanoma tumor. This tissue contains the naturally occurring TILs that will be used to create the personalized treatment.
Following the tumor resection, the collected tissue is shipped to a central manufacturing facility. At this facility, the TILs are separated from the tumor tissue and placed in a laboratory environment to grow and multiply over approximately three to four weeks. This results in a final product containing billions of the patient’s own T-cells.
Just before the patient is ready to receive their manufactured cells, they undergo a preparatory regimen in the hospital. This step involves a short course of chemotherapy known as lymphodepletion. This procedure temporarily reduces the number of other immune cells in the patient’s body, which helps create a more favorable environment for the newly infused TILs to function effectively.
The next step is the infusion of the lifileucel product itself. The patient receives their personalized army of TILs through a single intravenous (IV) infusion. This is a one-time treatment event where the billions of cancer-fighting cells are returned to the body to begin their work.
After the TIL infusion, patients receive a short course of interleukin-2 (IL-2), a protein that acts as a growth factor for T-cells. The IL-2 is administered to help stimulate the newly infused TILs, encouraging them to proliferate and actively attack cancer cells. This supportive therapy is an important part of ensuring the infused cells can establish themselves and mount an effective anti-tumor response.
Potential Side Effects and Safety Information
The lifileucel treatment regimen includes a Boxed Warning from the FDA, which highlights its most serious risks. Many of the side effects are not from the TIL cells themselves but are associated with the other required components of the therapy. The lymphodepleting chemotherapy and the high-dose interleukin-2 (IL-2) administered after the infusion contribute to the treatment’s safety profile.
Common adverse reactions reported by patients undergoing the treatment include chills, fever, fatigue, and gastrointestinal issues. Patients may also experience a rapid heart rate, known as tachycardia, and these side effects are generally managed in the hospital setting.
The Boxed Warning specifically points to more severe potential complications. These include treatment-related mortality, prolonged severe low blood cell counts (cytopenia), severe infection, and cardiopulmonary and renal impairment.