Adoptive Cell Therapy Less Effective in Pretreated Metastatic Melanoma

By Reuters Staff

August 25, 2021

NEW YORK (Reuters Health) - Patients with metastatic melanoma that has relapsed following anti-PD-1 therapies or BRAF/MEK inhibitors may not respond as well to adoptive cell transfer of tumor-infiltrating lymphocytes (ACT-TIL) as those who have never received these treatments, new research suggests.

With ACT-TIL, autologous tumor-infiltrating lymphocytes are taken from a patient's tumor, grown in the laboratory, and then given back to the patient to help fight their cancer. Tumors exposed to prior treatments, including newer immunotherapies and targeted therapies, may yield fewer or less robust lymphocytes for the ACT-TIL to be effective.

"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. 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," Dr. Stephanie Goff of the National Cancer Institute, in Bethesda, Maryland, said in a news release.

The researchers took a look back at the outcomes of 226 metastatic melanoma patients who participated in four clinical trials of ACT-TIL; 83% of the patients had relapsed on a prior therapy.

The objective response rate after ACT-TIL was 24% among patients who had received prior anti-PD-1 therapy compared to 56% (P=0.0006) among patients who had never received anti-PD-1 therapy (but might have received other therapies).

Among patients who received prior MAPK inhibitors, the objective response rate was 21% compared to 60% in MAPK inhibitor-naive patients (P=0.0057).

Median progression-free survival was 6.5 months among patients who had never received anti-PD-1 therapy versus 3.2 months in those who had received anti-PD-1 therapy (P<0.0001). In patients who received prior MAPK inhibitors, median progression-free survival was 2.5 months, compared to 6.6 months in MAPK inhibitor-naïve patients (P=0.0001).

The results appear in Clinical Cancer Research, a journal of the American Association for Cancer Research.

These data "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. We should think about utilizing TILs earlier in the disease course," Dr. Goff said in the release.

The data also suggest that harvesting treatment-naive lymphocytes before a patient tries other therapies may be worthwhile, 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," Dr. Goff said.

The study was funded by the National Cancer Institute and a cooperative research and development agreement with Iovance Biotherapeutics. The authors have declared no relevant conflicts of interest.

SOURCE: https://bit.ly/3D4juv3 Clinical Cancer Research, online August 19, 2021.

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