European researchers announced on Saturday that a new treatment for advanced melanoma was more effective than the existing main therapy in a phase 3 clinical trial.
The treatment, which uses a patient’s own immune cells to fight the cancer, has some similarities to another type of treatment that has been shown to be very effective for blood cancers, called CAR-T therapy.
CAR-T therapy involves harvesting a patient’s T cells and modifying them in the lab to turn them into cancer fighters, then injecting the cells back into the patient. Personalized treatment was first shown to be effective a decade ago in some leukemia patients; it is now also used for lymphomas as well as multiple myeloma.
And although it has been explored for solid tumors, which make up the majority of cancers, including melanoma, these tumors present challenges that blood cancers do not. Many blood cancers are homogeneous, which means their cells are uniform. This gives CAR-T therapy a clear target to latch onto and attack. But solid tumors tend to have a number of different cell types that vary widely between cancer types, said Dr. Vincent Lam, an assistant professor of oncology at Johns Hopkins Medicine who specializes in immunotherapies.
This tumor cell heterogeneity makes it difficult to find a practical and universal CAR-T target in solid tumors, said Lam, who was not involved in the new research.
In the melanoma trial, doctors used an approach called TIL therapy. This involves harvesting a patient’s immune cells – in this case, cells called tumour-infiltrating lymphocytes, which are taken from the tumor – but instead of modifying them in the lab as they would with CAR-T therapy, they are simply amplified to produce billions of cells.
These cells are then injected back into the patient’s bloodstream, where they can work to kill the cancer.
“We are expanding them from one million cells to several billion cells,” Dr. John Haanen, a medical oncologist at the Netherlands Cancer Institute, who led the new clinical trial, told NBC News.
Haanen presented the results of the trial – the first of its kind to test TIL therapy against an existing treatment – at the ESMO Congress 2022 meeting in Paris.
“That’s what the field needs to really gain confidence in this emerging therapy. It’s potentially changing practice,” Lam said of the findings.
In the trial, 168 patients with metastatic melanoma were randomly assigned to receive either TIL treatment or the current standard treatment, an immunotherapeutic drug called ipilimumab. Ipilimumab is typically used in people who don’t respond to a first-line treatment called anti-PD-1 therapy; almost all of the patients in the trial did not respond to this treatment.
Patients were followed for a median of nearly three years. Compared to those treated with ipilimumab, patients on TIL treatment experienced a 50% reduction in disease progression and death.
In the TIL group, 20% saw their tumors disappear completely, compared to 7% in the ipilimumab group. Patients are still being followed, but so far the overall median survival time for cancer patients who received TIL treatment was more than two years, compared to just over 1.5 years for those receiving ipilimumab. If a patient is able to go into full remission, the chances of it lasting for years are high, Haanen said.
“For a population that has already failed treatment, this is very good news,” he said.
According to Dr. Michael Davies, chair of melanoma medical oncology at MD Anderson Cancer Center in Houston, TIL therapy has been used in clinical trials to treat melanoma for nearly two decades, but it was the first to compare to an approved drug head to head. The kicker is that it turned out superior.
“This is the first time we’ve achieved such a result with cell therapy immunotherapy for melanoma patients,” said Davies, who serves on the scientific advisory board of Iovance Biotherapeutics, a California-based company that conducts research. phase 2 trial of TIL therapy in patients with melanoma who have failed anti-PD-1 therapy.
Melanoma rates have risen rapidly in the United States over the past 30 years, and although metastatic melanoma, the most severe stage of the disease, in which the cancer has spread to other parts of the body, is relatively rare, it is often fatal.
But treatment options for patients with metastatic melanoma have changed dramatically over the past decade, with the development of drugs called checkpoint inhibitors, including ipilimumab and anti-PD-1 treatments. These drugs deploy a person’s natural immune cells in an attack on tumor cells. However, if patients do not respond to these treatments, additional treatment options are few.
Melanoma, however, is particularly suitable for TIL therapy, said Dr. Steve Rosenberg, chief of the surgical branch of the National Cancer Institute in Bethesda, Maryland. Compared to other solid cancers, melanoma tumors have a particularly large number of mutations that are the targets of tumor-infiltrating lymphocytes.
“This approach can work in many types of cancer, but for tumors other than melanoma, selecting the right TIL to use is critical. Melanoma is unique because you can use all TILs without selection,” said Rosenberg, who first proposed TIL therapy in the 1980s.
By itself, the therapy causes very few side effects and none that are long-lasting, Haanen said. However, for it to be effective, TIL therapy must be used in combination with chemotherapy and another drug called interleukin-2, or IL-2, both of which have extensive side effects.
“When you introduce billions of cells, you can’t just add them to the body, you have to make room, and chemotherapy does that by killing the cells,” Haanen said. Then, once the patient is infused with their own lab-grown cells, IL-2 helps the new cells survive.
Rosenberg cautioned that the trial results can only be applied to metastatic melanoma, but added that there is a growing body of research exploring TIL therapy for other solid cancers, including lung and cancer. of the cervix.
TIL therapy is also likely still years away from being approved for use outside of clinical trials, which would open it up to many more patients with metastatic melanoma. Several US-based companies are also investigating TIL therapy.
“There’s more to cell therapy than we first thought,” Haanen said. “It opens up a whole new world of treatment options for the future.”
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