An experimental treatment for advanced melanoma is poised to be the next major breakthrough in cancer treatment, experts say.
Results from a phase 3 clinical trial published in the New England Journal of Medicine on Wednesday showed the treatment, which uses a superconcentrate boost of the person’s own immune cells, was more effective than the existing main treatment in putting patients in remission.
The trial, led by researchers in the Netherlands, caps a decade of astonishing progress in treating metastatic melanoma, a disease that just over a decade ago had a 5-year survival rate of only 5%.
The new approach, called TIL therapy, uses immune cells harvested from the tumor itself to fight the cancer. The cells are called tumor-infiltrating lymphocytes – the “TIL” in TIL therapy.
“These are immune cells that are in the tumor, trying to kill the tumor, but obviously not doing a good enough job because the tumor is growing,” said Dr. Patrick Hwu, president and CEO of the Moffitt Cancer Center in Tampa. , Florida.
To supercharge the cells, they are taken to a laboratory where they are multiplied until they number in the billions – an army now formidable enough to attack the tumor.
How TIL held up
The new clinical trial included 168 patients with advanced melanoma, almost all of whom had previously tried and failed to respond to a first-line treatment called anti-PD-1 therapy. (Ahead of Wednesday’s release, the results were presented in September at the European Cancer Meeting ESMO Congress 2022 in Paris.)
In the trial, half of the patients received TIL therapy and the other half an immunotherapeutic drug called ipilimumab. After treatment, patients were followed for a median of 33 months.
According to the study, those who received TIL therapy saw their disease progression and mortality decrease by 50%, compared to those who were treated with ipilimumab.
The therapy did not work for all participants.
Just under half, 49%, of TIL patients experienced at least partial remission – meaning at least a 30% decrease in their metastatic tumors – compared with 21% of patients who received ipilimumab.
More surprising was that 20% of TIL patients had complete remissions – all of their tumors had disappeared – a result that was “better than we expected”, said Dr John Haanen, a medical oncologist at the Netherlands Institute of Cancer. cancer, in a statement. E-mail.
In the ipilimumab group, 7% experienced complete remission.
“Patients in complete remission have an excellent prognosis,” he said. “We estimate that more than 80% of them could be cured.”
Hwu did not participate in the Dutch trial, but is conducting his own research into TIL therapy and has had equally impressive results.
“I have patients that we treated with TIL therapy ten years ago and they’re not getting any treatment right now, they’re just living normal lives,” he said.
A last ditch effort
Bruce Hawley, 64, of Ocala, Florida, had already undergone several rounds of immunotherapy for his advanced melanoma when he agreed to try TIL therapy as a last resort. By then, the cancer, which had started at the bottom of her foot, had spread throughout her body.
He enrolled in a clinical trial studying TIL therapy at Moffitt.
There, doctors harvested the TILs from Hawley’s tumor and multiplied them into the billions.
But before the concentrated infusion of cancer-fighting cells could be pumped back into Hawley’s bloodstream, he needed chemotherapy to free up space for the billions of incoming cells.
“Chemotherapy destroys immune cells to make room for TIL cells,” Hwu said.
Along with the infusion of billions of TILs, patients also receive interleukin-2, which is a growth factor that supports new cells and helps them proliferate, he said.
Hwu added that while infusion of TILs doesn’t cause many side effects in patients, chemotherapy and interleukin-2 do.
TIL therapy is not yet commercially available, although the Moffitt Cancer Center is one of several research institutes who worked with Iovance Biotherapeutics, a California-based biotech company that is on track to seek Food and Drug Administration approval for its TIL therapy product.
Jen Saunders, director of investor relations and public relations at Iovance, said the company is in the process of submitting its results to the FDA and approval could possibly come in the second half of next year. .
Improvements in melanoma treatments
Melanoma is the most dangerous form of skin cancer, and for decades metastatic melanoma – that is, cancer that has spread to other parts of the body – was considered a death sentence.
“I used to call the melanoma clinic ‘the sad clinic,'” said Dr. Hussein Tawbi, a melanoma oncologist at MD Anderson Cancer Center in Houston, who was not involved in the new research. “It’s not that anymore. There’s so much hope, there’s so much promise. We can do so much for these patients.”
This shift has occurred over the past 10 years, researchers reported Tuesday in the journal JAMA Network Open. From 2013 to 2017, death rates from metastatic melanoma fell for the first time in 40 years.
The improved survival may be linked to FDA approval of several new treatments for the disease, including ipilimumab, beginning in 2011, the study authors wrote. These new treatments have increased a person’s chance of surviving five years after a diagnosis of metastatic melanoma from 5% to more than 50%.
Cell therapy for other types of cancer
One of the most striking results of the new clinical trial was complete remission in one-fifth of patients who received TIL treatment. In other words, their tumors completely disappeared.
“If you have complete regression due to TIL therapy, that seems to me to be curative,” said Dr. Steven Rosenberg, chief of surgery at the National Cancer Institute in Bethesda, Maryland.
He was not involved in the last trial, but his view prevails in the cancer community: he was the first to use TIL therapy in patients. In a 1988 article published in the New England Journal of Medicine, he and his colleagues described how TIL therapy could shrink a patient’s metastatic melanoma tumors.
Some of those patients from 1988, Rosenberg said, are still alive. According to him, other patients he has treated with TIL therapy have been cancer-free for 20 years.
The difference between his research on TIL therapy and the new clinical trial, he said, is that the clinical trial directly compared TIL to another treatment — and found that it worked better.
I think it is this type of cell therapy that is the most exciting area of modern cancer treatment.
Dr Steven Rosenberg
The treatment isn’t just promising for melanoma patients.
“I think it’s this type of cell therapy that is the most exciting area of modern oncology treatment,” Rosenberg said. He compared the potential of TIL therapy to that of another type of cancer treatment that has revolutionized the way certain blood cancers are treated.
This treatment is CAR-T therapy. Similar to TIL therapy, it involves harvesting immune cells and later injecting them back into the body to fight cancer. Unlike TILs, the cells used in CAR-T therapy must be genetically modified in the laboratory before returning to the patient.
The hope is that TIL therapy will also be used for other solid cancers, not just melanoma, Rosenberg said. Solid cancers — any type of cancer that forms a lump in the body, such as lung, breast or colon cancer — account for 90% of all cancer deaths, he said.
The use of TIL therapy for other cancers than metastatic melanoma requires further work. With melanoma, all of the TILs extracted from the tumor will work to fight the cancer. For other cancers, however, the approach only works if cells are selected that recognize the cancer, he said.
Dr George Coukos, an oncologist at the University Hospital of Lausanne and the Ludwig Institute for Cancer Research in Switzerland, said in an email that there is early evidence that TIL therapy may also work against d other tumors, including lung cancer, as well as cancers caused by HPV (human papillomavirus), which includes cervical cancer and anal cancer.
Iovance Biotherapeutics is also studying TIL therapy for these cancers, according to Saunders. Other researchers and companies are also working on TIL therapy products, she said.
In Hwu’s lab at the Moffitt Cancer Center, researchers continue to study TIL.
“I think we could potentially, in the long term, develop TIL from almost any tumor type, he said. “And the reason we study it so hard in my lab is because the therapy TIL will be a game changer for many people. types of cancer. »
Hawley, from Florida, said he would have died without TIL therapy. He received the treatment in December 2018. His melanoma tumors shrank for about two years, he said. In 2021, he noticed another growth – one that his surgeon was able to remove completely.
“They said, from what we could see, we got it, we got it all figured out,” he said.
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