On February 16, 2024, the U.S. Food and Drug Administration (FDA) approved the first tumor-infiltrating lymphocyte (TIL) cancer therapy for metastatic melanoma, lifileucel (Amtagvi™). Patients in the drug’s clinical trial experienced a significant decrease in tumor burden, and the median overall survival was 17.4 months.

This ONS resource was produced for educational purposes only. Refer to the full lifileucel prescribing information for all details. 

ClassificationTumor-derived autologous T-cell immunotherapy; tumor-infiltrating lymphocyte therapy
Mechanism of ActionLifileucil’s exact mechanism of action is unknown. In general, TIL therapies use T cells collected directly from the tumor and the cells are manufactured with the drug interleukin-2 (IL-2) to create cells that easily identify, navigate to, and fight the cancer specifically.
IndicationAdults diagnosed with metastatic or unresectable melanoma who have previously been treated with an anti–PD-1 antibody or a BRAF inhibitor, with or without MKI inhibitor if positive for a BRAF V600 variant.
Dosing, Frequency, and Duration
  • A single dose contains between 7.5 × 109 and 72 × 109 cells divided into four individual infusion bags of 100–125 ml each, housed in protective metal cassettes.
  • The treatment is for autologous use only; patient information must match identifiers on drug cassettes and infusion bags.
  • Administer in an inpatient hospital setting with access to cardiopulmonary support or critical care.
  • Preadministration: 
    • Two days prior to infusion, administer lymphodepleting cyclophosphamide and fludarabine via IV.
    • Infuse lifileucel 24–96 hours following the final dose of fludarabine.
    • Premedicate with diphenhydramine 30–60 minutes prior to lifileucel infusion. 
  • During administration:
    • Thaw and administer one bag of lifileucel at a time if more than one bag is provided.
    • Infuse 1 ml per minute for the first 5 minutes, then increase to 5–10 ml per minute thereafter.
    • After infusing the final bag, rinse the tubing and flush with normal saline at the same rate to ensure the entire product was given.
  • Postadministration:
    • 3–24 hours post infusion, administer IV IL-2 every 8–12 hours for a maximum of six doses to bolster the action of manufactured T cells. 
RouteIV infusion
Safe HandlingLifileucel does not meet the definition of a hazardous drug; however, no carcinogenicity or genotoxicity studies have been performed and its effects on fertility are unknown. Follow institutional handling precautions and local biosafety regulations to prevent infectious disease transmission.

Black box warnings  

  • Cardiopulmonary and renal impairment
  • Prolonged severe cytopenia
  • Severe infection 
  • Treatment-related mortality

Other warnings 

  • Hypersensitivity reaction


  • Severe cytopenias (including thrombocytopenia, lymphopenia, neutropenia, and leukopenia) lasting for 30 days or longer occurred in 45.5% of patients in lifileucel’s clinical trials.
  • Infection of any grade, including severe, life-threatening, or fatal, occurred in 26.9% of patients.


  • Tachycardia, atrial fibrillation, arrhythmia, acute myocardial infarction, cardiac ventricular thrombosis, cardiomyopathy, QT prolongation, and other cardiac disorders occurred in 9% of patients.


  • Acute reactions (e.g., fever, rigors, chills, tachycardia, rash, hypotension, dyspnea, cough, chest tightness, wheezing) generally occurred and resolved within one day of infusion.

Multisystem organ hemorrhage

  • In the treatment’s clinical trials, intrabdominal and intracranial hemorrhage was associated with two deaths.
  • Patients with thrombocytopenia must not use anticoagulants and must be monitored closely.

Additional monitoring

  • Signs of respiratory failure
  • Signs of acute renal injury or failure
  • Diarrhea, nausea, or vomiting
  • Laboratory abnormalities (e.g., thrombocytopenia, neutropenia, anemia, leukopenia, lymphopenia, hypophosphatemia)
  • Monitor patients’ baseline cardiopulmonary and renal status, perform pregnancy testing, and review patients’ blood panels. 
  • Test patients for chronic viral infection, including cytomegalovirus, hepatitis B or C, and HIV.
  • Confirm lymphodepletion with cyclophosphamide and fludarabine.
  • Premedicate patients with diphenhydramine 30–60 minutes prior to infusion.
  • Do not use a leukocyte depleting filter during administration.
  • Avoid systemic steroids, which may impede lifileucel’s effect.
  • Patients must be hospitalized before, during, and after administration.
  • Ensure IL-2 is available prior to lifileucel administration.
  • Verify patient’s identity and match identifiers to the drug cassettes and infusion bags.
  • Thaw and administer one bag at a time. Use room temperature water and break up clumps by inverting or massaging the bag. Inspect the bag for signs of leakage.
  • Monitor patient for signs of hypersensitivity and treat as needed. 
  • Give six doses of IL-2 to enhance the efficacy of the cellular product.
  • Closely monitor patients for hemorrhage, hypersensitivity reactions, and infection.
  • Educate patients about possible side effects of treatment.
  • Instruct patients to report symptoms such as:
    • Diarrhea
    • Fast or irregular heartbeat
    • Low blood pressure
    • Rash
    • Signs of bleeding
    • Signs of infection (e.g., fever, chills, fatigue, low white blood cell count)
  • Remind patients to remain within a two-hour drive of the treatment site for several weeks after treatment.
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