Older melanoma patients respond better to immunotherapy

June 13 (UPI) — Anti-PD1 immunotherapy was more effective in treating older melanoma patients in a recent study, according to researchers who see potential in better targeting the therapy to younger patients.

Researchers found that in each decade, the likelihood of progression of melanoma after treatment with anti-programmed cell death receptor-1 decreased by 13 percent. Their findings were published Tuesday in Clinical Cancer Research, a journal of the American Association for Cancer Research.

Melanoma, a type of cancer, develops from the pigment-containing cells known as melanocytes typically in the skin. With 22.1 cases per 100,000 men and women, melanomas of the skin are ranked fifth, behind female breast cancer, prostate, lung and colon/rectum, according to the Centers for Disease Control and Prevention. It is not in the top 10 cancers by rate of death.

“We have shown that the characteristics of the aged tumor microenvironment in older patients promote resistance to melanoma targeted therapies, highlighting the importance of considering patient age when predicting response to therapy,” Dr. Ashani Weeraratna, a co-leader of the Immunology, Microenvironment and Metastasis Program at The Wistar Institute in Philadelphia, said in a press release.

In past research, Weeraratna and colleagues had shown that the tumor microenvironment in older patients promoted melanoma metastasis and resistance to targeted therapy with a BRAF inhibitor.

“We wanted to study how the aging microenvironment affects response to immunotherapy, and much to our surprise, the effect was exactly the opposite of what we learned with targeted therapy,” Weeraratna said in an AACR press release.

The researchers analyzed medical records from 538 patients with melanoma who were treated with pembrolizumab, generally known as Keytruda, at eight medical facilities.

Nearly half of the patients — 238 — were younger than 62 years.

Researchers report that 50 percent of patients younger than 62 had poor response to the treatment, compared with only 37 percent of patients 62 years or older. This finding was independent of gender or prior treatment with MAPK inhibitors.

“Interestingly, younger patients who had prior MAPKi therapy had a much lower rate of complete response to anti-PD1 than older patients who had prior MAPKi therapy — 4 percent versus 15 percent,” Weeraratna said.

To gain a better understanding of the initial results, and attempt to repeat them, the researchers studies mice with with melanoma — finding the results matched those from human patients. And further research revealed differences in the immune microenvironment of the two groups of mice.

When combining anti-PD1 with an anti-CD25 antibody therapy, they found it yielded response rates comparable to those seen in older mice.

The scientists, analyzing primary and metastatic melanoma samples from another 268 patients, found age-related differences in the T-cell subpopulations within the tumors of these patients.

“Our results suggest that preconditioning the tumor microenvironment in younger patients by depleting Tregs could make them respond to anti-PD1 immunotherapies better,” Weeraratna said. “Our studies suggest that in designing therapies for melanoma, age should be considered as a factor in both preclinical and clinical models.”

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