A new form of immunotherapy called tumor-infiltrating lymphocyte (TIL) therapy is offering hope to some patients with metastatic melanoma who have few remaining treatment options.
Melanoma is an uncommon but serious form of skin cancer: While melanoma makes up only 1 percent of skin cancer diagnoses in the United States, it causes the majority of deaths from skin cancer. That was especially true before 2011, when surgery was most patients’ only option for treatment and life expectancy for people with metastatic melanoma was just six to eight months.
“In 2011, new drugs called PD-1 and CTLA-4 inhibitors were approved that changed the landscape,” says UNC Health surgical oncologist David Ollila, MD. “It was astounding. A large randomized trial demonstrated that for 49 percent of melanoma patients, there was a seven-and-a-half year survival rate with these treatments.”
That, of course, leaves about half of metastatic melanoma patients who do not benefit from these medications, which are a form of immunotherapy because they target specific parts of the immune system. For this group, TIL therapy is emerging as a new option.
When you have a tumor, your immune system produces TILs, which are immune cells, to attack the tumor, but sometimes they’re not enough to completely destroy a tumor. With TIL therapy, a part of your tumor is harvested for TILs; then billions of them are grown in a lab and infused back into you. This high quantity of TILs might be able to stop tumor growth, shrink the tumor or destroy it entirely.
“Right now, it’s very high risk, high reward,” says UNC Health hematologist and oncologist Felicia Cao, MD, PhD. “You have to go through a long process for TIL therapy, you’re at risk of infection, and we can’t predict which people will respond to this treatment. But there’s a possibility of long-term response.”
Drs. Cao and Ollila answer common questions about this treatment, which is available at UNC Health.
How does TIL therapy work?
TIL therapy starts with surgery to remove a part of your tumor. Depending on where the tumor is, that may be relatively easy or, if major organs are affected, a more complicated and invasive surgery. Then, the tumor is sent to a laboratory that will harvest your TILs from that tumor and grow more of them.
“With CAR T-cell therapy, another form of immunotherapy, your cells are genetically modified, but with TIL, nothing is modified,” Dr. Cao says. “We just have to try to grow more of what’s already there.”
That’s the first point of uncertainty in this process: not every sample will produce enough new TILs for further treatment. Dr. Cao says about 10 percent of samples do not yield enough TILs.
While your TILs are growing in number, a process that takes about four to six weeks, you’ll recover from the surgery and prepare to receive the TIL infusion.
“We give the patient chemotherapy, not to treat the cancer, but to make spaces for the billions of cells we’ll give to you,” Dr. Cao says. “This is a chemotherapy with a lot of side effects—nausea, fatigue, hair loss—and because melanoma rarely requires chemotherapy, many patients aren’t used to this.”
Right now, this chemotherapy requires in-patient admission to UNC because of its intensity and the high risk for infection.
After chemotherapy, you’ll receive the infusion of TIL cells. Dr. Cao says that this part has few side effects, but the next part has many.
“We give you injections of interleukin-2 (IL-2) to support the activity of the TILs over three days in the intensive care unit,” Dr. Cao says. IL-2 is a cytokine, or a protein, that helps to regulate the immune system and will encourage the TILs to do their work. “This is where there can be a lot of side effects. It feels like a very bad flu, with fever, shaking and chills. We can give you meds to try to help, but you may not be able to receive all six planned doses.”
After the IL-2 injections are done, you can leave the hospital, but you’ll be asked to stay close by for a few weeks for monitoring and because of the risk of infection.
A few months after your TIL therapy, you’ll have scans to see if the treatment shrunk or destroyed your tumor.
Who is a candidate for TIL therapy?
Right now, TIL therapy is only approved for people with melanoma that hasn’t responded to other treatments, but not everyone will be able to tolerate this process.
“It’s hard to get an older patient with a lot of comorbidities, like past heart surgeries or diabetes, through this process,” Dr. Ollila says. “It’s better for younger patients who are relatively healthy, other than their metastatic melanoma.”
Patients must tolerate uncertainty and waiting, as not everyone can get enough TILs for the infusion, and not everyone has a robust response.
“It’s still no guarantee, but there’s not another choice right now,” Dr. Ollila says. “It’s both a last shot and a chance for a home run.”
If you have melanoma that hasn’t responded to other treatments and are generally healthy, look for a Center of Excellence in TIL therapy, such as UNC Health. The staff at these centers have received special training in this therapy.
“It’s a big process, and we ask a lot of these patients,” Dr. Cao says. “It takes a lot of time out of your life compared to other treatments, but there is support from our teams. There are a lot of people working together to help you through.”
Those teams include medical and surgical oncologists skilled in the treatment of melanoma, doctors from the cellular therapy program, nurse navigators and social workers. The team also includes people to help with the insurance authorization process. While TIL therapy is a Food and Drug Administration-approved therapy and typically covered by insurance, both Dr. Cao and Dr. Ollila note that the approval process can be lengthy.
What happens after TIL therapy?
After TIL therapy, you’ll need time to recover from the effects of the chemotherapy and IL-2 injections, and the TILs need time to do their work on the tumor. It won’t be clear if the therapy worked or how well it worked for a few months.
“Right now, about 65 to 70 percent of people have a response, which means about a third of people won’t respond at all to the therapy,” Dr. Cao says. “Of those who do respond, 10 to 15 percent have such a great response that they may not need any other treatment. About 30 to 40 percent respond with noticeable tumor shrinking. For some, the tumor doesn’t shrink but the disease remains stable for longer, which can be a great thing.”
The oncologists are clear with patients about the possibilities and realities of the treatment.
“It’s great when it works, and we see results on that first or second scan,” Dr. Ollila adds. “It can give people life. But there’s no guarantee, it’s not easy and it doesn’t mean the melanoma won’t come back at some point.”
Drs. Cao and Ollila hope the treatment will become easier with time, and Dr. Cao notes that TIL therapy is in clinical trials for lung cancer and cervical cancer.
“Down the line, I think we’ll be able to make better predictions about which patients will respond to this,” Dr. Cao says. “Right now, it won’t work for everyone, but it does offer hope.”
For more information on cancer treatments, talk to your doctor. If you need a doctor, find one near you.