By Ted Rosen, MD
The U.S. Food and Drug Administration (FDA) recently approved a truly transformational therapy, Lilileucel (Amtagvi,Iovance Biotherapeutics), designed for unresectable or metastatic malignant melanoma previously treated with other modalities. Prior failure of immune checkpoint inhibitors (PD-1 blocking antibodies) or of a BRAF inhibitor (with or without a concurrent MEK inhibitor) is a prerequisite to receive this novel cellular immunotherapy. This new treatment is especially appropriate for patients who are facing a dismal prognosis and have few – if any – remaining therapeutic options.
Individuals who undergo Amtagvi treatment first undergo preconditioning with high doses of lymphocyte-depleting chemotherapy. This induces the production of homeostatic cytokines (growth factors) which promote expansion of the lymphocyte pool. From a cubic centimeter of the patient’s own neoplasm, tumor-infiltrating lymphocytes are extracted and re-introduced via infusion. It is then hoped that the tumor-specific cytotoxic T-lymphocytes will attack the cancer.
This process received FDA approval based upon promising results from a 73 patient Phase 2 clinical trial. Fully 31.5% of patients exhibited an objective response, including 4.1% with a complete response and 27.4% with a partial response. The impressive results centered around persistence of response. Among those who were responsive, 56.5%, 47.8% and 43.5% continued without tumor progression or death for six, nine and twelve month periods, respectively. A larger, confirmatory Phase 3 study is already underway.
While Amtagvi will not be needed for most of our melanoma patients, it offers hope for a subset of such patients who generally face about a 35% five-year survival rate.
Ted Rosen, MD, is a Professor of Dermatology at Baylor College of Medicine in Houston and the Medical Editor of the Dermatology Digest.
