February 21, 2024

Pioneering cell-based treatment for melanoma offered at Siteman Cancer Center

Siteman Cancer Center, located at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, is among the pioneering institutions nationwide to introduce a recently approved cell-based immunotherapy designed for melanoma.

With the green signal from the Food and Drug Administration (FDA), physicians at Siteman Cancer Center will deliver tumor-infiltrating lymphocyte (TIL) therapy to certain adult patients grappling with metastatic melanoma, a formidable skin cancer that has spread to other body parts. This therapy targets patients with metastatic melanoma ineligible for surgical intervention, who have experienced continued growth and spread despite undergoing extensive prior treatments, including chemotherapy and immune checkpoint inhibitors.

Washington University clinicians and researchers played a pivotal role in the clinical trials leading to FDA approval.

The immunotherapy gained approval under Accelerated Approval regulations, permitting the FDA to greenlight drugs for severe illnesses or conditions lacking adequate medical solutions. To secure approval, these drugs must demonstrate an effect indicative of probable clinical benefit to patients�such as improving their well-being or extending survival. The Accelerated Approval pathway typically enables patients to access promising therapies while further trials confirm the drug's clinical benefits.

At Siteman, physicians, researchers, and patients remain actively engaged in ongoing clinical trials exploring TIL therapy's efficacy for advanced lung and cervical cancers. Developed by Iovance Therapeutics, the newly approved TIL therapy is named lifileucel (trade name Amtagvi).

TIL therapy utilizes a patient's own T cells, which have homed in on and infiltrated the tumor in an effort to combat the cancer. However, these innate cancer-fighting immune cells require support, as they are scarce and swiftly overwhelmed by tumors.

"This represents truly personalized cancer therapy, as the T cells are derived from the patient's own tumor," remarked surgical oncologist Ryan C. Fields, MD. "These T cells are already programmed in multiple ways to target the specific cancer cells. Moreover, since the T cells are the patient's own, there's no risk of immune cells attacking healthy tissues�a perilous scenario known as graft-versus-host disease, which can occur with stem cell transplantation for blood cancers."

The Cutaneous Oncology Program, housed within Washington University's Division of Oncology and co-led by Ansstas, Fields, and Lynn A. Cornelius, MD, will oversee TIL therapy administration for eligible melanoma patients.

For this therapy, physicians at an authorized treatment center extract a tumor sample and send it to an Iovance manufacturing facility. Here, tumor-infiltrating lymphocytes are isolated from the tumor, expanded outside the body, and cryopreserved. The resulting TIL therapy cell product is then shipped back to the patient. Upon intravenous infusion, these tumor-specific T cells, now numbering in the billions, exhibit enhanced efficacy in targeting tumor cells throughout the body. Patients undergo chemotherapy to prepare their bodies for T cell infusion, alongside interleukin-2 treatment to bolster T cell activity.

According to findings from a clinical trial published in The Journal for ImmunoTherapy of Cancer, approximately 30% of patients witnessed at least a 30% reduction in tumor size. Furthermore, around half of patients experiencing tumor response to the therapy achieved a remission lasting at least 12 months post-single TIL treatment.

The treatment regimen involves chemotherapy to eliminate existing T cells and create room for the new T cells to thrive, stimulating an intensified immune response. This process may trigger various side effects, including heightened infection risk, internal bleeding, cardiac arrhythmias, respiratory and kidney failure, and allergic reactions. While many side effects are manageable, some may pose severe, life-threatening risks. Consequently, the initial rollout of TIL therapy is occurring at centers with substantial experience in treating patients with cell-based immunotherapies, such as CAR-T cell therapy for blood cancers.