Prior Immunotherapy May Impact Melanoma Treatment Response

Prior immunotherapy treatments in patients with advanced melanoma can lead to influenced responses in PD-1 blockade immunotherapy.

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In a recent study,¹ researchers from the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center aggregated data from 7 clinical cohorts of patients with advanced melanoma. These patients (n=514) had all received immune checkpoint inhibitor (ICI) therapy. Following melanoma tumor biopsies, they had all either undergone exome sequencing (WES), RNA-sequencing, or matched WES and RNA-sequencing. However, through the process of exclusion, the study later involved a total of 427 patients.

Researchers also collected demographic information from the cohorts, including age, melanoma subtype, original study cohort, point in time therapy was received, prior CLTA-4 blockade therapy status, RECIST 1.1 response to therapy, sex, and treatment regimen.

Past treatment regimens included anti-CTLA-4 monotherapy, anti-PD-1 monotherapy, or combination or sequential therapies involving both therapies. Participants had either had tumor biopsies with WES (n=284) or RNA-sequencing (n=442). Of these, 188 patients had tumor biopsies involving matched WES and RNA-sequencing.

As a result of the study and cohort data analysis, researchers made note of several findings, including:

• Tumor mutational burden (TMB) was associated with anti-PD-1 benefits in patients with a history of anti-CTLA-4 treatment. In fact, TMB was significantly higher in cutaneous melanoma biopsies than in other origins, including mucosal, acral, or uveal. TMB was also significantly higher in biopsies of patients with a history of anti-CTLA-4 treatment responses.
• Prior CTLA-4 blockade use, with and without a response to anti-PD-1, differentially stratified the melanoma tumor expression landscape.
• Inflammatory gene expression strength in anti-PD-1 was associated with prior anti-CTLA-4 blockade use.
• Globally, increased adaptive immune infiltration signatures were associated with anti-CTLA-4 use.

"We undertook this project to establish a resource for other researchers, with the goal of identifying statistically significant correlates of melanoma responses to anti-PD-1 therapy,” said Katie Campbell, PhD and lead study author, in a press release.²

Campbell noted that the greatest differences became evident when researchers accounted for patients’ history of prior treatment with an anti-CTLA-4 blockade.

“The context in which a biopsy is collected needs to be considered to better define how biomarkers should be implemented in the clinical setting,” Campbell said.

References

1. Campbell KM, Amouzgar M, Pfeiffer SM, et al. Prior anti-CTLA-4 therapy impacts molecular characteristics associated with anti-PD-1 response in advanced melanoma. Cancer Cell. 2023;41(4). doi:10.1016/j.ccell.2023.03.010
2. University of California, Los Angeles (UCLA), Health Sciences. Prior treatments influence immunotherapy response in advanced melanoma. Newswise. https://www.newswise.com/articles/prior-treatments-influence-immunotherapy-response-in-advanced-melanoma. Published April 10, 2023. Accessed April 17, 2023.