Tumor-infiltrating lymphocyte therapy treats tumors on a large scale

A new treatment strategy with personalized cell therapy significantly improves progression-free survival compared to standard immunotherapy in patients with advanced melanoma, according to the groundbreaking results reported at the ESMO 2022 Congress from the phase 3 M14TIL study.

“This study shows for the first time in a randomized controlled trial that cell therapy can be effective and beneficial for patients with solid tumors,” said lead author John Haanen, Netherlands Cancer Institute, Amsterdam, The Netherlands. “For patients with melanoma, we see a 50% reduction in the chance of disease progression or death from the disease, which absolutely means changing the practice. This is the first time a TIL-based approach has been directly compared. with standard-of-care, in this case ipilimumab. So now we are able to position TIL treatment much better in the management landscape for patients with metastatic melanoma. ”

“TIL therapy is an extraordinary therapy,” commented George Coukos, University Hospital of Lausanne and Ludwig Institute for Cancer Research, Lausanne, Switzerland, who was not involved in the study. “TIL is a new paradigm for cancer treatment and, as these results clearly demonstrate, it is effective and feasible on a large scale. The results raise hopes for the management and potential cure of metastatic solid cancers.”

Treatment essentially involves taking a small sample from a patient’s resected tumor, growing immune T cells from the tumor in the laboratory, and then infusing the patient with personalized TIL therapy after chemotherapy. TILs recognize cancer cells as abnormal, penetrate them, and then work to kill them.

The Phase 3 M14TIL trial randomized 168 patients with unresectable stage IIIC-IV melanoma to immunotherapy with the anti-CTLA-4 antibody ipilimumab or treatment with TIL; most of the patients had failed previous anti-PD-1 treatment. Results first reported at the 2022 ESMO Congress showed that patients treated with TIL therapy had a significantly longer median progression-free survival of 7.2 months compared to 3.1 months in those treated with ipilimumab; the overall response rate to TILs was 49% versus 21% for ipilimumab; the median overall survival was 25.8 months versus 18.9 months. Patients are still being followed up for overall survival.

Treatment options for patients with metastatic melanoma have changed considerably over the past 10 years with the development of checkpoint inhibitors, including the PD-1 inhibitors nivolumab and pembrolizumab and the CTLA-4 inhibitor ipilimumab. These drugs release a natural brake on the immune system so that the body’s immune cells can recognize and attack cancer cells. “They have a very good safety profile and fairly high efficacy and are now often given as first-line therapy. But if patients fail first-line treatments, the options become very scarce, particularly for patients who fail first-line treatments. anti-PD-1 drugs, so there is a real unmet need, ”explained Haanen. She added: “In our study, 89% of patients had failed anti-PD-1 treatment.” The remaining patients joined the study before anti-PD-1 therapies were authorized.

Exploring the possible mechanism by which TIL therapy is effective in patients who have failed anti-PD-1 treatment, Haanen suggested: “We think the anti-PD-1 treatment resistance mechanism is mainly provided by the tumor microenvironment. So when we take these cells out of their natural environment, reactivate them in the lab, grow them to a very large number and return them to patients we can overcome some of the escape mechanisms and that’s what we’re seeing, otherwise the TILs wouldn’t work. in this environment. ”

Although Grade 3 or greater adverse events occurred in all patients treated with TIL therapy and in 57% of those randomized to ipilimumab, Haanen said: “Side effects are well manageable and most resolve by the time they go. which patients leave the hospital after TIL therapy “. She also added that most of the side effects are related to other therapies, including chemotherapy and interleukin-2, which patients receive as part of the TIL regimen. Regarding the impact of TIL therapy, Haanen concluded: “TIL has the potential to benefit patients with a wide range of solid tumors and studies are currently underway on many cancers, including lung, neck and neck cancers. ‘uterus and head and neck “.

Haanen explained that the trial was conducted by academics in the Netherlands and Denmark, without the involvement of industry. Researchers are now working to get EMA approval for their TIL therapy to try to ensure it remains affordable, free from commercial pressures.

“The results of this phase 3 study could potentially lead to regulatory approval that would change the practice,” said Coukos. “It would allow countries that would consider this path to create centers capable of providing TIL therapy to patients and to establish this potential second-line treatment in advanced melanoma.”


European Society of Medical Oncology


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