lifileucel (Amtagvi); tumor-infiltrating lymphocyte therapy

Indications

• unresectable or metastatic melanoma (accelerated approval 2024)
  • previously treated with a PD-1 blocking antibody
    • if BRAF V600 mutation positive, also treated with a BRAF inhibitor with or without a MEK inhibitor

Dosage

• dose is 7.5-72 x 10E9 viable cells suspended in 1-4 patient infusion bags
• administer in hospital setting with an intensive care unit
• administer lymphocyte-depleted regimen prior to lifileucel
• do not use leukocyte depleting filter when administering lifileucel
• premedicate with acetaminophen, or equivalent, & diphenhydramine, or another H1-antihistamine
• administer IL-2 (aldesleukin) after infusion of lifileucel

Adverse effects

• in order of frequency
  • chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash, hypotension, alopecia, infection, hypoxia, dyspnea
• severe
  • prolonged severe cytopenia
  • internal organ hemorrhage

Mechanism of action

• autologous T-cell immunotherapy

Notes

• cancer cells can sabotage tumor-infiltrating lymphocytes by filling them with defective mitochondria rendering them less able to divide & more likely to commit apoptosis
• tumor-infiltrating lymphocytes cultured with cancer cells containing fluorescent- tagged mitochondria took on some faulty mitochondria after only 24 hours
  • by 15 days, lymphocyte native mitochondria had been replaced almost entirely

More general terms

• chimeric antigen-receptor (CAR) T-cell therapy