Saturday, April 13

New cell-based therapy for melanoma more effective than existing treatment, trial finds

European researchers announced Saturday that a new treatment for advanced melanoma was more effective than the leading existing 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 proven to be highly 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 infusing the cells back into the patient. The personalized treatment was first shown to be successful a decade ago in certain leukemia patients; it’s now also used for lymphomas as well as multiple myeloma.

And while it’s 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, meaning 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 largely between cancer types, said Dr. Vincent Lam, an assistant professor of oncology at Johns Hopkins Medicine, who specializes in immunotherapies.

This heterogeneity of the tumor cells makes finding a convenient and universal CAR-T target difficult in solid tumors, said Lam, who was not involved with the new research.

In the melanoma trial, doctors used an approach called TIL therapy. It involves harvesting a patient’s immune cells — in this case, cells called tumor-infiltrating lymphocytes, which are taken from the tumor — but instead of modifying them in the lab as they would with CAR-T therapy, they’re simply amplified to produce billions of cells.

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Those cells are then infused back into the patient’s bloodstream, where they can work to kill the cancer.

“We expand them from a 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.

“This is what the field needs to really gain confidence about this emerging therapy. It’s potentially practice-changing,” Lam said of the results.

In the trial, 168 patients with metastatic melanoma were randomly assigned to receive either TIL treatment or the current standard treatment, an immunotherapy drug called ipilimumab. Ipilimumab is typically used in people who don’t respond to a first-line treatment called anti-PD-1 therapy; nearly all of the patients in the trial had not responded to that treatment.

The patients were followed for a median of almost three years. Compared to those who were treated with ipilimumab, patients on TIL therapy had a 50% reduction in disease progression and death.

In the TIL therapy group, 20% saw their tumors disappear completely, compared to 7% in the ipilimumab group. The patients are still being tracked, but so far, the median overall time of survival for cancer patients who received TIL therapy was over two years, compared to just over 1.5 years for those receiving ipilimumab. If a patient is able to get into complete remission, the chances that it will last years are high, Haanen said.

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“For a population that has already failed one treatment, this is very good news,” he said.

According to Dr. Michael Davies, chair of melanoma medical oncology at the MD Anderson Cancer Center in Houston, TIL therapy has been used in clinical trials to treat melanoma for nearly two decades, but this was the first one to compare it to an approved drug head-to-head. The kicker is that it was found to be superior.

“It’s the first time that we’ve had a result like that with a cell therapy immunotherapy for patients with melanoma,” said Davies, who is on the scientific advisory board for Iovance Biotherapeutics, a California-based company that is conducting a Phase 2 trial on TIL therapy in melanoma patients who failed anti-PD-1 treatment.

Melanoma rates have been rising rapidly in the United States over the past 30 years, and although metastatic melanoma, the most serious stage of the disease, in which the cancer has spread to other parts of the body, is relatively rare, it’s often fatal.

But treatment options for patients with metastatic melanoma have changed considerably over the last 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 therapy options are scarce.

Melanoma, however, is uniquely suited for TIL therapy, said Dr. Steve Rosenberg, chief, Surgery Branch at the National Cancer Institute in Bethesda, Maryland. Compared to other solid cancers, melanoma tumors have a particularly large number of mutations that are targets of the tumor-infiltrating lymphocytes.

“This approach can work in many cancer types, but for tumors other than melanoma it is essential to select the right TIL to use. Melanoma is unique because you can use all TIL without selection,” said Rosenberg, who was the first person to propose TIL therapy in the 1980s.

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By itself, the therapy causes very few side effects and none that are long-lasting, Haanen said. However, in order for it to be effective, TIL therapy must be used in conjunction with chemotherapy and another drug called interleukin-2, or IL-2, which both have wide-reaching side effects.

“When you introduce billions of cells, you cannot just add them to the body, you have to make space, and the chemotherapy does that by killing off cells,” Haanen said. Then, once the patient receives the infusion of their own, lab-grown cells, the IL-2 helps the new cells survive.

Rosenberg cautioned that the results of the trial 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 cervical cancers.

TIL therapy is also still likely years away from being approved for use outside clinical trials, which would open it up to many more patients with metastatic melanoma. Multiple US-based companies are also studying TIL therapy.

“There is more to cell therapy than we thought at the beginning,” Haanen said. “It opens up a whole new world of treatment options for the future.”

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