PD‐L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study
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. Met...
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| Veröffentlicht in: | The oncologist (Dayton, Ohio) Ohio), 2020-03, Vol.25 (3), p.e520-e527 |
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| creator | 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 |
| description | 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.
The objective of this study was to determine whether PD‐L1 expression on circulating tumor cells can serve as a predictive biomarker of clinical benefit and response to treatment with the PD‐1 inhibitor pembrolizumab. |
| doi_str_mv | 10.1634/theoncologist.2019-0557 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7066715</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2376729039</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3875-5f681d0019ab66869cb00123b1ecced95567109ccb37f01c10878414d102d9773</originalsourceid><addsrcrecordid>eNqNkc9u1DAQxiMEoqXwCuAjlxQ7juOYA1IJ5Y-0ZVdQJG6W40y2Ro692M7CcuIFkHhGngSvWgq9IVnyjPzNbzzzFcUjgo9JQ-sn6QK80976tYnpuMJElJgxfqs4JKwWZS3wx9s5xi0tOWHioLgX4yeMc0iru8UBrUhTtVgcFj9WL359_7kg6PTrJkCMxjuUT2eCnq1Kxq3R-Tz5gDqwNqIztUPPAa0CDEYnswXkR_QO4sa7CCh5tIKpD96ab_OkemQcOhm2ymkY0BlY5fyknu71s00RjcFPSKGVsT6h92kedveLO6OyER5c3UfFh5en593rcrF89aY7WZSatpyVbGxaMuRxhOqbpm2E7nNS0Z6Azq0EYw0nWGjdUz5iovMeeFuTeiC4GgTn9Kh4dsndzP0EgwaXgrJyE8ykwk56ZeTNF2cu5NpvJcdNRrMMeHwFCP7zDDHJyUSdV6Qc-DnKivKGVwJTkaX8UqqDjzHAeN2GYLk3U94wU-7NlHszc-XDf395XffHvb9jfDEWdv_Llcu33ZJQ0jL6G8-otog</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2376729039</pqid></control><display><type>article</type><title>PD‐L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><source>Access via Oxford University Press (Open Access Collection)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>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</creator><creatorcontrib>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</creatorcontrib><description>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.
The objective of this study was to determine whether PD‐L1 expression on circulating tumor cells can serve as a predictive biomarker of clinical benefit and response to treatment with the PD‐1 inhibitor pembrolizumab.</description><identifier>ISSN: 1083-7159</identifier><identifier>EISSN: 1549-490X</identifier><identifier>DOI: 10.1634/theoncologist.2019-0557</identifier><identifier>PMID: 32162809</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; Circulating tumor cells ; Humans ; Immunotherapy ; Immuno‐Oncology ; Melanoma ; Melanoma - drug therapy ; Neoplastic Cells, Circulating ; Pembrolizumab ; Pilot Projects</subject><ispartof>The oncologist (Dayton, Ohio), 2020-03, Vol.25 (3), p.e520-e527</ispartof><rights>2019 The Authors. published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.</rights><rights>2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3875-5f681d0019ab66869cb00123b1ecced95567109ccb37f01c10878414d102d9773</citedby><cites>FETCH-LOGICAL-c3875-5f681d0019ab66869cb00123b1ecced95567109ccb37f01c10878414d102d9773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066715/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066715/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,27924,27925,45574,45575,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32162809$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khattak, Muhammad A.</creatorcontrib><creatorcontrib>Reid, Anna</creatorcontrib><creatorcontrib>Freeman, James</creatorcontrib><creatorcontrib>Pereira, Michelle</creatorcontrib><creatorcontrib>McEvoy, Ashleigh</creatorcontrib><creatorcontrib>Lo, Johnny</creatorcontrib><creatorcontrib>Frank, Markus H.</creatorcontrib><creatorcontrib>Meniawy, Tarek</creatorcontrib><creatorcontrib>Didan, Ali</creatorcontrib><creatorcontrib>Spencer, Isaac</creatorcontrib><creatorcontrib>Amanuel, Benhur</creatorcontrib><creatorcontrib>Millward, Michael</creatorcontrib><creatorcontrib>Ziman, Melanie</creatorcontrib><creatorcontrib>Gray, Elin</creatorcontrib><title>PD‐L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study</title><title>The oncologist (Dayton, Ohio)</title><addtitle>Oncologist</addtitle><description>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.
The objective of this study was to determine whether PD‐L1 expression on circulating tumor cells can serve as a predictive biomarker of clinical benefit and response to treatment with the PD‐1 inhibitor pembrolizumab.</description><subject>Antibodies, Monoclonal, Humanized</subject><subject>B7-H1 Antigen</subject><subject>Circulating tumor cells</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Immuno‐Oncology</subject><subject>Melanoma</subject><subject>Melanoma - drug therapy</subject><subject>Neoplastic Cells, Circulating</subject><subject>Pembrolizumab</subject><subject>Pilot Projects</subject><issn>1083-7159</issn><issn>1549-490X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxiMEoqXwCuAjlxQ7juOYA1IJ5Y-0ZVdQJG6W40y2Ro692M7CcuIFkHhGngSvWgq9IVnyjPzNbzzzFcUjgo9JQ-sn6QK80976tYnpuMJElJgxfqs4JKwWZS3wx9s5xi0tOWHioLgX4yeMc0iru8UBrUhTtVgcFj9WL359_7kg6PTrJkCMxjuUT2eCnq1Kxq3R-Tz5gDqwNqIztUPPAa0CDEYnswXkR_QO4sa7CCh5tIKpD96ab_OkemQcOhm2ymkY0BlY5fyknu71s00RjcFPSKGVsT6h92kedveLO6OyER5c3UfFh5en593rcrF89aY7WZSatpyVbGxaMuRxhOqbpm2E7nNS0Z6Azq0EYw0nWGjdUz5iovMeeFuTeiC4GgTn9Kh4dsndzP0EgwaXgrJyE8ykwk56ZeTNF2cu5NpvJcdNRrMMeHwFCP7zDDHJyUSdV6Qc-DnKivKGVwJTkaX8UqqDjzHAeN2GYLk3U94wU-7NlHszc-XDf395XffHvb9jfDEWdv_Llcu33ZJQ0jL6G8-otog</recordid><startdate>202003</startdate><enddate>202003</enddate><creator>Khattak, Muhammad A.</creator><creator>Reid, Anna</creator><creator>Freeman, James</creator><creator>Pereira, Michelle</creator><creator>McEvoy, Ashleigh</creator><creator>Lo, Johnny</creator><creator>Frank, Markus H.</creator><creator>Meniawy, Tarek</creator><creator>Didan, Ali</creator><creator>Spencer, Isaac</creator><creator>Amanuel, Benhur</creator><creator>Millward, Michael</creator><creator>Ziman, Melanie</creator><creator>Gray, Elin</creator><general>John Wiley & Sons, Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>202003</creationdate><title>PD‐L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3875-5f681d0019ab66869cb00123b1ecced95567109ccb37f01c10878414d102d9773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antibodies, Monoclonal, Humanized</topic><topic>B7-H1 Antigen</topic><topic>Circulating tumor cells</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Immuno‐Oncology</topic><topic>Melanoma</topic><topic>Melanoma - drug therapy</topic><topic>Neoplastic Cells, Circulating</topic><topic>Pembrolizumab</topic><topic>Pilot Projects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khattak, Muhammad A.</creatorcontrib><creatorcontrib>Reid, Anna</creatorcontrib><creatorcontrib>Freeman, James</creatorcontrib><creatorcontrib>Pereira, Michelle</creatorcontrib><creatorcontrib>McEvoy, Ashleigh</creatorcontrib><creatorcontrib>Lo, Johnny</creatorcontrib><creatorcontrib>Frank, Markus H.</creatorcontrib><creatorcontrib>Meniawy, Tarek</creatorcontrib><creatorcontrib>Didan, Ali</creatorcontrib><creatorcontrib>Spencer, Isaac</creatorcontrib><creatorcontrib>Amanuel, Benhur</creatorcontrib><creatorcontrib>Millward, Michael</creatorcontrib><creatorcontrib>Ziman, Melanie</creatorcontrib><creatorcontrib>Gray, Elin</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The oncologist (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khattak, Muhammad A.</au><au>Reid, Anna</au><au>Freeman, James</au><au>Pereira, Michelle</au><au>McEvoy, Ashleigh</au><au>Lo, Johnny</au><au>Frank, Markus H.</au><au>Meniawy, Tarek</au><au>Didan, Ali</au><au>Spencer, Isaac</au><au>Amanuel, Benhur</au><au>Millward, Michael</au><au>Ziman, Melanie</au><au>Gray, Elin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PD‐L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study</atitle><jtitle>The oncologist (Dayton, Ohio)</jtitle><addtitle>Oncologist</addtitle><date>2020-03</date><risdate>2020</risdate><volume>25</volume><issue>3</issue><spage>e520</spage><epage>e527</epage><pages>e520-e527</pages><issn>1083-7159</issn><eissn>1549-490X</eissn><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.
The objective of this study was to determine whether PD‐L1 expression on circulating tumor cells can serve as a predictive biomarker of clinical benefit and response to treatment with the PD‐1 inhibitor pembrolizumab.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>32162809</pmid><doi>10.1634/theoncologist.2019-0557</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE; Access via Oxford University Press (Open Access Collection); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Antibodies, Monoclonal, Humanized B7-H1 Antigen Circulating tumor cells Humans Immunotherapy Immuno‐Oncology Melanoma Melanoma - drug therapy Neoplastic Cells, Circulating Pembrolizumab Pilot Projects |
| title | PD‐L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study |
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