PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study

PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab. Blood samples...

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Published in:The oncologist (Dayton, Ohio) Ohio), 2019-12
Main Authors: Khattak, Muhammad A, Reid, Anna, Freeman, James, Pereira, Michelle, McEvoy, Ashleigh, Lo, Johnny, Frank, Markus H, Meniawy, Tarek, Didan, Ali, Spencer, Isaac, Amanuel, Benhur, Millward, Michael, Ziman, Melanie, Gray, Elin
Format: Article
Language:English
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Summary:PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab. Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1. CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1 CTCs (14/25, 64%) had significantly longer progression-free survival (PFS) compared with patients with PD-L1 CTCs (26.6 months vs. 5.5 months; = .018). The 12-month PFS rates were 76% versus 22% in the PD-L1 versus PD-L1 CTCs groups ( = .012), respectively. A multivariate linear regression analysis confirmed that PD-L1 CTC is an independent predictive biomarker of PFS (hazard ratio, 0.229; 95% confidence interval, 0.052-1.012; = .026). Our results reveal the potential of CTCs as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with melanoma. PD-L1 expression on CTCs may be predictive of response to pembrolizumab and longer PFS. The present data suggest that PD-L1 expression on circulating tumor cells may predict response to pembrolizumab in advanced melanoma. This needs further validation in a larger trial and, if proven, might be a useful liquid biopsy tool that could be used to stratify patients into groups more likely to respond to immunotherapy, hence leading to health cost savings.
ISSN:1549-490X