Muhammad A Khattak1,2,3, Anna Reid2, James Freeman2, Michelle Pereira2, Ashleigh McEvoy2, Johnny Lo4, Markus H Frank2,5,6, Tarek Meniawy3,7, Ali Didan1, Isaac Spencer2, Benhur Amanuel8, Michael Millward3,7, Melanie Ziman2,3, Elin Gray9. 1. Department of Medical Oncology, Fiona Stanley Hospital, Australia. 2. School of Medical and Health Sciences, Edith Cowan University, Perth, Australia. 3. Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Australia. 4. School of Engineering, Edith Cowan University, Joondalup, Australia. 5. Transplantation Research Program, Boston Children's Hospital and Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 6. Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA. 7. Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia. 8. Department of Anatomical Pathology, PathWest, Australia. 9. School of Medical and Health Sciences, Edith Cowan University, Perth, Australia e.gray@ecu.edu.au.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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; p = .018). The 12-month PFS rates were 76% versus 22% in the PD-L1+ versus PD-L1- CTCs groups (p = .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; p = .026). CONCLUSION: 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. IMPLICATIONS FOR PRACTICE: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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; p = .018). The 12-month PFS rates were 76% versus 22% in the PD-L1+ versus PD-L1- CTCs groups (p = .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; p = .026). CONCLUSION: 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. IMPLICATIONS FOR PRACTICE: 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.
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Authors: Paul Winograd; Shuang Hou; Colin M Court; Yi-Te Lee; Pin-Jung Chen; Yazhen Zhu; Saeed Sadeghi; Richard S Finn; Pai-Chi Teng; Jasmin J Wang; Zhicheng Zhang; Hongtao Liu; Ronald W Busuttil; James S Tomlinson; Hsian-Rong Tseng; Vatche G Agopian Journal: Hepatol Commun Date: 2020-08-04