Patients in South Florida diagnosed with metastatic melanoma will soon have access to the first cellular therapy for this advanced form of skin cancer, following its recent approval by the Food and Drug Administration (FDA). The therapy, known as tumor-infiltrating lymphocyte therapy, or TIL, uses patients’ own immune cells to battle their cancer. It will be available to patients at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine as South Florida’s only center offering this treatment.

According to a Centers for Disease Control and Prevention (CDC) 2020 report, Florida has the second highest number of new melanoma cases per year in the U.S.

Additionally, Sylvester researchers will be part of an upcoming clinical trial led by TIL’s manufacturer, Iovance Biotherapeutics, to determine if certain modifications to the therapy can improve its effectiveness for even more patients.

Trials testing the TIL therapy, called lifileucel (Amtagvi®, Iovance Biotherapeutics), which was granted accelerated approval by the US Food and Drug Administration (FDA) in early 2024, showed a response rate of 32% among 153 patients before formal drug approval. [1][2]

Today, lifileucel, a tumor-derived autologous T-cell immunotherapy, for adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor, is approved for patients whose melanoma has progressed despite treatment with other forms of immunotherapy, including those involving checkpoint inhibitors, and targeted therapy for melanomas with a common mutation in the BRAF gene.

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Major breakthrough
“Cellular therapy represents a major breakthrough in the battle against advanced melanoma,” noted Jose Lutzky, M.D., skin-cancer specialist and director of Cutaneous Oncology Services at Sylvester.

“The trial results offer hope to our patients with this potentially deadly disease,” Lutzky added.

He also noted that in the clinical trial that led to lifileucel’s approval, more than half of patients who responded favorably to the therapy had maintained that response for over three years.

Although TIL therapy has been studied in labs and clinical trials for decades, lifileucel represents the first FDA approval for any TIL treatment.

Unleashing the Immune Response
Tumor-infiltrating lymphocytes or TILs are naturally occurring immune cells composed of a mix of white blood cells, T cells and B cells that invade tumors to try to fight them. To boost their natural cancer-killing abilities, TIL therapy involves surgically removing a patient’s tumor, isolating the lymphocytes within it and then growing them in larger quantities at a special manufacturing facility before reinfusing them into the patient.

Unlike other types of cell therapy, such as CAR T-cell therapy, the lymphocytes are not genetically engineered to recognize cancer because they are already attuned to the patient’s specific tumor. The TIL method also involves treatments after infusion to activate and stimulate the lymphocytes within the patient’s body.

Lutzky said the therapy, which typically includes surgery, high doses of chemotherapy before infusion and subsequent treatments can take its toll on patients, and those with heart conditions or other health problems may be unable to tolerate the treatment.

“These are not easy treatments, but many patients do have great responses,” he explained.

Upcoming Clinical Trial
Lutzky plans to begin enrollment for Sylvester’s participation in the phase 2 Iovance trial soon and hopes to enroll 10 or more patients in the next year. Eligible participants will be patients with advanced melanoma whose previous treatments failed against the disease.

The trial will test a variation of TIL therapy in which immune cells are genetically engineered to remove a gene called PD-1, which acts as a natural block on immune cell activity. Cancerous cells often hijack this process to switch off the body’s immune cells.

“Removing PD-1 from lymphocytes may enhance their cancer-killing ability in the body,” Lutzky explained.

“Laboratory studies and an early-stage clinical trial of these modified cells showed that they are just as active as the non-engineered lymphocytes,” Lutzky said.

The Journey to Treatment Breakthroughs
Before joining Sylvester, Lutzky participated in clinical trials that led to FDA approval of another immunotherapy for metastatic melanoma — a checkpoint inhibitor called ipilimumab. In fact, melanoma was the first cancer for which checkpoint inhibitors were approved as a treatment.

Because melanoma response is closely tied to the immune system, immunotherapies tend to work better with this cancer than other types. Moreover, lessons learned from treating melanoma with immunotherapy have enabled researchers and clinicians to apply those findings to fight other cancers, Lutzky noted.

“Melanoma was the first tumor where checkpoint inhibitors were found to be effective and established what we now call the fourth pillar of cancer treatment, adding immunotherapy to surgery, chemotherapy and radiation,” he added.

“It’s been a really amazing journey.”

Clinical trials
A Study to Investigate the Efficacy and Safety of an Infusion of IOV-4001 in Adult Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer – ClinicalTrials.gov ID NCT05361174

Highlights of prescribing information
Lifileucel (Amtagvi®, Iovance Biotherapeutics)[Prescribing information]

Reference
[1] Keam SJ. Lifileucel: First Approval. Mol Diagn Ther. 2024 Apr 16. doi: 10.1007/s40291-024-00708-y. Epub ahead of print. PMID: 38625642.
[2] Parums DV. Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi). Med Sci Monit. 2024 May 1;30:e944927. doi: 10.12659/MSM.944927. PMID: 38689550.

Photo caption and courtesy
Cell therapy has now become a viable option for patients with advanced melanoma. The trial results represent a major advancement for our patients, noted Jose Lutzky, M.D., a skin cancer physician and director of cutaneous oncology at Sylvester Comprehensive Cancer Center. Photo courtesy © 2024 by Sylvester Comprehensive Cancer Center.

 

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