This is a dramatic shift from the way we’ve treated solid tumors."
Novant Health is now offering TIL (tumor-infiltrating lymphocytes) therapy for people with advanced melanoma for whom certain immunotherapy and targeted therapies are no longer effective. Novant is the only center in Western North Carolina currently able to provide the breakthrough treatment, called lifileucel (Amtagvi), which is one of the first cellular therapies approved for a solid tumor.
“We are at an inflection point in the era of immunotherapy for treating cancer,” said David Rizzieri, MD, physician in chief and senior vice president of the Novant Health Cancer Institute. “It continues the theme of harnessing the power of one’s own immune system to directly kill cancer cells.”
Lifileucel is currently being investigated in clinical trials at Novant in partnership with Iovance Biotherapeutics for patients with non-small-cell lung and some gynecologic cancers.
“For almost every solid tumor type, there is now a role for immunotherapy in some way, shape or form,” said Garrett Sherwood, MD, medical oncologist at Novant Health. “It’s the most significant advancement in solid tumor oncology in the last 30 years.”
A novel type of immunotherapy
Despite successful outcomes in many cases, most patients treated with currently available immunotherapy drugs will eventually stop responding. TIL therapy uses the patient’s own T-cells to hopefully stimulate a greater immune response against their cancer.
“The reason patients stop responding to current immunotherapy treatments is not necessarily because the lymphocyte no longer recognizes the tumor as foreign, but because the tumor has engaged multiple mechanisms in which it can evade those lymphocytes, or the lymphocytes can get exhausted,” said Dr. Sherwood. “The constant stimulation creates a situation where they are no longer able to effectively kill the cancer cells. By extracting the T-cells that have already located the tumor and exponentially expanding them, we believe we can overcome these resistance mechanisms. This represents a dramatic shift from the way we’ve treated solid tumors.”
What patients can expect
The process takes six to eight weeks with two weeks in the hospital. Surgeons first acquire tumor tissue where the lymphocytes reside and then send the tissue specimen to a specialized lab where the lymphocytes are extracted and grown.
The patient then receives chemotherapy to remove the ineffective lymphocytes and then the newly generated lymphocytes are reinfused. Afterward, the patient receives high dose IL-2, an immunotherapy drug that facilitates the TIL activity. The patient remains in the ICU with intense monitoring.
“After that intense process, all we do is follow those patients,” said Dr. Sherwood. “We let them recover, check on them every few weeks to see how they’re doing. But there are no more infusions, and there’s no more chemo. At that point, we’re hoping we’ve retrained the immune system to attack and control the cancer.”
Clinical trial data
Lifileucel was approved by the FDA in February 2024. Safety and efficacy were evaluated in patients with unresectable or metastatic melanoma who had previously been treated with at least one systemic therapy, including a PD-1 blocking antibody, and if BRAF V600 mutation-positive, a BRAF inhibitor with or without a MEK inhibitor.
The objective response rate among patients treated with lifileucel was 31.5% (95% confidence interval, 21.1%–43.4%), including three (4.1%) complete responses and 20 (27.4%) partial responses. Among the responders (n = 23), 56.5%, 47.8%, and 43.5% maintained durable responses at 6, 9, and 12 months, respectively.
“With TIL therapy, if we can regenerate that initial immune-versus-tumor response, then those patients can go into prolonged, sustained remission,” said Dr. Sherwood. “The early data showed the promise of long-term disease control without ongoing infusions.”
Dr. Sherwood noted that the majority of otherwise healthy melanoma patients who stopped responding to treatment will need TIL treatment at some point in their cancer journey. “And lung cancer is just one step behind melanoma,” he said.
“When standard therapies are failing patients, then newer modalities like TIL have an immediate role,” said Dr. Rizzieri. “They are quickly moving up in the lines of therapy as we get better data on safety and durability, and I could see a point in the future where they may be first-line therapy.”
To refer a patient for TIL therapy, please call 866-611-3722.