Sooner Rather than Later Might be Watchword for Experimental Metastatic Melanoma Treatment

The use of lymphocytes to attack tumors may be less effective if given after other treatments, study published in an AACR journal indicates.

Sooner rather than later may be the best strategy for using an experimental treatment for advanced melanoma, according to a study published in the AACR journal Clinical Cancer Research.  

The treatment, known as adoptive cell transfer of tumor-infiltrating lymphocytes, or ACT-TIL, seemed to be more effective if it was given to patients with metastatic melanoma before, rather than after, they were treated with powerful new immunotherapies or molecularly targeted therapies, according to the study. Currently, ACT-TIL is given after the patient develops resistance to the other treatments.  

“While ACT-TIL is a strategy now pursued solely for patients with treatment-refractory metastatic melanoma, we believe these data suggest that ACT-TIL could be considered as a front-line strategy for select patients,” wrote Stephanie Goff, MD, an associate research physician in the Surgery Branch of the National Cancer Institute of the National Institutes of Health and lead author of the published report.  

Melanoma is the most dangerous form of skin cancer, especially when it spreads beyond the skin to other organs of the body, such as the lungs. Treatments developed in recent years include therapies that help the body’s own immune system attack the melanoma cells, called anti-PD1-therapies, and drugs targeted at genetic components of the melanoma tumors, called MAPK inhibitors. 

ACT-TIL works by using immune cells known as lymphocytes that are removed from the patient’s circulatory system, grown to much greater quantities in the laboratory, and given back to the patient to attack the tumors.  

“We noticed, over the last few years, we were seeing fewer responses to ACT-TIL in metastatic melanoma patients, which coincided with these newer therapies coming on board,” Goff said. “We wanted to see if there were differences in responses between those who had received prior immunotherapy or targeted therapies and those who did not.” 

Goff and her colleagues studied the outcomes of 226 patients from four completed clinical trials of ACT-TIL, 83 percent of whom had disease that relapsed on a prior therapy. They examined differences in response based on characteristics such as age, sex, tumor size and location, and prior treatments.  

Some 56 percent of patients who hadn’t received anti-PD-1 immunotherapy responded to the ACT-TIL treatment, while the response rate fell to 24 percent among those who had gotten the immunotherapy, the study showed.  Similarly, 60 percent of patients who hadn’t received MAPK targeted therapy responded to the lymphocytes, while only 21 percent of those who received the targeted therapy responded to ACT-TIL.  

“The data in this manuscript demonstrate that if you wait to use ACT-TIL as a later-line therapy, you may not get the same durable responses as when you use it up front,” Goff said.  “We should think about utilizing TILs earlier in the disease course.”  

Since the TILs are taken originally from the patients’ own bodies, exposing them to prior treatments may pose some hurdles, Goff said. These may include yielding fewer or less robust lymphocytes than needed for the ACT-TIL to be effective, Goff explained. 

According to Goff, these data present an argument for harvesting lymphocytes before a patient tries other therapies, so that ACT-TIL is available if the patient relapses. 

“If we harvest the lymphocytes before they’ve seen any medications, we could potentially develop it into an effective later-line therapy with better response rates,” she said.