Loading…
PD-L1 Expression Is Low in Large B-Cell Lymphoma with MYC or Double-Hit Translocation
Introduction: In large B-cell lymphoma (LBCL) MYC translocation and MYC/BCL2 or BCL6 double hit (DH) is associated with poor prognosis and there is an unmet need for novel treatment targets in this patient group. Treatment targeting the PD-L1/PD-1 pathway has been successfully introduced in Hodgkin...
Saved in:
Published in: | Blood 2018-11, Vol.132 (Supplement 1), p.4113-4113 |
---|---|
Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c1976-28ae7dbcf1175eb168240ea1dfddc64ddd3b150427a477304bca4137fa3b2ec13 |
---|---|
cites | |
container_end_page | 4113 |
container_issue | Supplement 1 |
container_start_page | 4113 |
container_title | Blood |
container_volume | 132 |
creator | Elbæk, Mette Vestergaard Pedersen, Mette Ø Breinholt, Marie Fredslund Reddy, Anupama Love, Cassandra Clasen-Linde, Erik Knudsen, Helle Nielsen, Signe Ledou Gang, Anne Ortved Hogdall, Estrid Dave, Sandeep Norgaard, Peter H. |
description | Introduction: In large B-cell lymphoma (LBCL) MYC translocation and MYC/BCL2 or BCL6 double hit (DH) is associated with poor prognosis and there is an unmet need for novel treatment targets in this patient group. Treatment targeting the PD-L1/PD-1 pathway has been successfully introduced in Hodgkin lymphoma and solid cancers but are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL.
Material and Methods: MYC, BCL2 and BCL6 translocations were detected by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 patients had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. 24 patients overlapped, i.e. were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences.
Results: PD-L1 protein expression level was lower in patients with MYC translocation (n=42, median=3,3%, IQR 0,0-10,8) or DH (n=31, median=3,3%, IQR 0,0-10,0) compared to patients with no MYC translocation (n=35, median=16,7%, IQR 3,3-30,0) or DH (n=46, 13,3%, IQR 2,5-30,0), P=0.004 and P |
doi_str_mv | 10.1182/blood-2018-99-111956 |
format | article |
fullrecord | <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1182_blood_2018_99_111956</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497119402139</els_id><sourcerecordid>S0006497119402139</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1976-28ae7dbcf1175eb168240ea1dfddc64ddd3b150427a477304bca4137fa3b2ec13</originalsourceid><addsrcrecordid>eNp9kL1OwzAYRS0EEqXwBgx-AYM_x4mTBQnSQisFwdAOTJb_Qo3SuLIDpW9PS5mZ7nSOrg5C10BvAEp2q7sQLGEUSlJVBACqvDhBI8hZSShl9BSNKKUF4ZWAc3SR0gelwDOWj9DydUIawNPvTXQp-dDjecJN2GLf40bFd4cfSO26Dje79WYV1gpv_bDCz281DhFPwqfuHJn5AS-i6lMXjBr2kkt01qouuau_HaPl43RRz0jz8jSv7xtioBIFYaVywmrTAojcaShKxqlTYFtrTcGttZmGnHImFBcio1wbxSETrco0cwayMeJHr4khpehauYl-reJOApWHNPI3jTykkVUlj2n22N0Rc_tvX95FmYx3vXHWR2cGaYP_X_ADXp1sVA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>PD-L1 Expression Is Low in Large B-Cell Lymphoma with MYC or Double-Hit Translocation</title><source>ScienceDirect Journals</source><creator>Elbæk, Mette Vestergaard ; Pedersen, Mette Ø ; Breinholt, Marie Fredslund ; Reddy, Anupama ; Love, Cassandra ; Clasen-Linde, Erik ; Knudsen, Helle ; Nielsen, Signe Ledou ; Gang, Anne Ortved ; Hogdall, Estrid ; Dave, Sandeep ; Norgaard, Peter H.</creator><creatorcontrib>Elbæk, Mette Vestergaard ; Pedersen, Mette Ø ; Breinholt, Marie Fredslund ; Reddy, Anupama ; Love, Cassandra ; Clasen-Linde, Erik ; Knudsen, Helle ; Nielsen, Signe Ledou ; Gang, Anne Ortved ; Hogdall, Estrid ; Dave, Sandeep ; Norgaard, Peter H.</creatorcontrib><description>Introduction: In large B-cell lymphoma (LBCL) MYC translocation and MYC/BCL2 or BCL6 double hit (DH) is associated with poor prognosis and there is an unmet need for novel treatment targets in this patient group. Treatment targeting the PD-L1/PD-1 pathway has been successfully introduced in Hodgkin lymphoma and solid cancers but are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL.
Material and Methods: MYC, BCL2 and BCL6 translocations were detected by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 patients had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. 24 patients overlapped, i.e. were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences.
Results: PD-L1 protein expression level was lower in patients with MYC translocation (n=42, median=3,3%, IQR 0,0-10,8) or DH (n=31, median=3,3%, IQR 0,0-10,0) compared to patients with no MYC translocation (n=35, median=16,7%, IQR 3,3-30,0) or DH (n=46, 13,3%, IQR 2,5-30,0), P=0.004 and P<0,001 respectively (Fig.1). PD-L1 mRNA expression was also significantly lower in patients with MYC translocation or DH, P=0,001 and P=0,006 respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-GC-type compared to GC-type DLBCL, P= 0,004 and P=0,002 respectively.
Conclusions: We report a highly significant association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared to patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.
[Display omitted]
No relevant conflicts of interest to declare.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2018-99-111956</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>Blood, 2018-11, Vol.132 (Supplement 1), p.4113-4113</ispartof><rights>2018 American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1976-28ae7dbcf1175eb168240ea1dfddc64ddd3b150427a477304bca4137fa3b2ec13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006497119402139$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3549,27924,27925,45780</link.rule.ids></links><search><creatorcontrib>Elbæk, Mette Vestergaard</creatorcontrib><creatorcontrib>Pedersen, Mette Ø</creatorcontrib><creatorcontrib>Breinholt, Marie Fredslund</creatorcontrib><creatorcontrib>Reddy, Anupama</creatorcontrib><creatorcontrib>Love, Cassandra</creatorcontrib><creatorcontrib>Clasen-Linde, Erik</creatorcontrib><creatorcontrib>Knudsen, Helle</creatorcontrib><creatorcontrib>Nielsen, Signe Ledou</creatorcontrib><creatorcontrib>Gang, Anne Ortved</creatorcontrib><creatorcontrib>Hogdall, Estrid</creatorcontrib><creatorcontrib>Dave, Sandeep</creatorcontrib><creatorcontrib>Norgaard, Peter H.</creatorcontrib><title>PD-L1 Expression Is Low in Large B-Cell Lymphoma with MYC or Double-Hit Translocation</title><title>Blood</title><description>Introduction: In large B-cell lymphoma (LBCL) MYC translocation and MYC/BCL2 or BCL6 double hit (DH) is associated with poor prognosis and there is an unmet need for novel treatment targets in this patient group. Treatment targeting the PD-L1/PD-1 pathway has been successfully introduced in Hodgkin lymphoma and solid cancers but are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL.
Material and Methods: MYC, BCL2 and BCL6 translocations were detected by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 patients had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. 24 patients overlapped, i.e. were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences.
Results: PD-L1 protein expression level was lower in patients with MYC translocation (n=42, median=3,3%, IQR 0,0-10,8) or DH (n=31, median=3,3%, IQR 0,0-10,0) compared to patients with no MYC translocation (n=35, median=16,7%, IQR 3,3-30,0) or DH (n=46, 13,3%, IQR 2,5-30,0), P=0.004 and P<0,001 respectively (Fig.1). PD-L1 mRNA expression was also significantly lower in patients with MYC translocation or DH, P=0,001 and P=0,006 respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-GC-type compared to GC-type DLBCL, P= 0,004 and P=0,002 respectively.
Conclusions: We report a highly significant association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared to patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.
[Display omitted]
No relevant conflicts of interest to declare.</description><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kL1OwzAYRS0EEqXwBgx-AYM_x4mTBQnSQisFwdAOTJb_Qo3SuLIDpW9PS5mZ7nSOrg5C10BvAEp2q7sQLGEUSlJVBACqvDhBI8hZSShl9BSNKKUF4ZWAc3SR0gelwDOWj9DydUIawNPvTXQp-dDjecJN2GLf40bFd4cfSO26Dje79WYV1gpv_bDCz281DhFPwqfuHJn5AS-i6lMXjBr2kkt01qouuau_HaPl43RRz0jz8jSv7xtioBIFYaVywmrTAojcaShKxqlTYFtrTcGttZmGnHImFBcio1wbxSETrco0cwayMeJHr4khpehauYl-reJOApWHNPI3jTykkVUlj2n22N0Rc_tvX95FmYx3vXHWR2cGaYP_X_ADXp1sVA</recordid><startdate>20181129</startdate><enddate>20181129</enddate><creator>Elbæk, Mette Vestergaard</creator><creator>Pedersen, Mette Ø</creator><creator>Breinholt, Marie Fredslund</creator><creator>Reddy, Anupama</creator><creator>Love, Cassandra</creator><creator>Clasen-Linde, Erik</creator><creator>Knudsen, Helle</creator><creator>Nielsen, Signe Ledou</creator><creator>Gang, Anne Ortved</creator><creator>Hogdall, Estrid</creator><creator>Dave, Sandeep</creator><creator>Norgaard, Peter H.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20181129</creationdate><title>PD-L1 Expression Is Low in Large B-Cell Lymphoma with MYC or Double-Hit Translocation</title><author>Elbæk, Mette Vestergaard ; Pedersen, Mette Ø ; Breinholt, Marie Fredslund ; Reddy, Anupama ; Love, Cassandra ; Clasen-Linde, Erik ; Knudsen, Helle ; Nielsen, Signe Ledou ; Gang, Anne Ortved ; Hogdall, Estrid ; Dave, Sandeep ; Norgaard, Peter H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1976-28ae7dbcf1175eb168240ea1dfddc64ddd3b150427a477304bca4137fa3b2ec13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elbæk, Mette Vestergaard</creatorcontrib><creatorcontrib>Pedersen, Mette Ø</creatorcontrib><creatorcontrib>Breinholt, Marie Fredslund</creatorcontrib><creatorcontrib>Reddy, Anupama</creatorcontrib><creatorcontrib>Love, Cassandra</creatorcontrib><creatorcontrib>Clasen-Linde, Erik</creatorcontrib><creatorcontrib>Knudsen, Helle</creatorcontrib><creatorcontrib>Nielsen, Signe Ledou</creatorcontrib><creatorcontrib>Gang, Anne Ortved</creatorcontrib><creatorcontrib>Hogdall, Estrid</creatorcontrib><creatorcontrib>Dave, Sandeep</creatorcontrib><creatorcontrib>Norgaard, Peter H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elbæk, Mette Vestergaard</au><au>Pedersen, Mette Ø</au><au>Breinholt, Marie Fredslund</au><au>Reddy, Anupama</au><au>Love, Cassandra</au><au>Clasen-Linde, Erik</au><au>Knudsen, Helle</au><au>Nielsen, Signe Ledou</au><au>Gang, Anne Ortved</au><au>Hogdall, Estrid</au><au>Dave, Sandeep</au><au>Norgaard, Peter H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PD-L1 Expression Is Low in Large B-Cell Lymphoma with MYC or Double-Hit Translocation</atitle><jtitle>Blood</jtitle><date>2018-11-29</date><risdate>2018</risdate><volume>132</volume><issue>Supplement 1</issue><spage>4113</spage><epage>4113</epage><pages>4113-4113</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Introduction: In large B-cell lymphoma (LBCL) MYC translocation and MYC/BCL2 or BCL6 double hit (DH) is associated with poor prognosis and there is an unmet need for novel treatment targets in this patient group. Treatment targeting the PD-L1/PD-1 pathway has been successfully introduced in Hodgkin lymphoma and solid cancers but are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL.
Material and Methods: MYC, BCL2 and BCL6 translocations were detected by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 patients had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. 24 patients overlapped, i.e. were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences.
Results: PD-L1 protein expression level was lower in patients with MYC translocation (n=42, median=3,3%, IQR 0,0-10,8) or DH (n=31, median=3,3%, IQR 0,0-10,0) compared to patients with no MYC translocation (n=35, median=16,7%, IQR 3,3-30,0) or DH (n=46, 13,3%, IQR 2,5-30,0), P=0.004 and P<0,001 respectively (Fig.1). PD-L1 mRNA expression was also significantly lower in patients with MYC translocation or DH, P=0,001 and P=0,006 respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-GC-type compared to GC-type DLBCL, P= 0,004 and P=0,002 respectively.
Conclusions: We report a highly significant association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared to patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.
[Display omitted]
No relevant conflicts of interest to declare.</abstract><pub>Elsevier Inc</pub><doi>10.1182/blood-2018-99-111956</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0006-4971 |
ispartof | Blood, 2018-11, Vol.132 (Supplement 1), p.4113-4113 |
issn | 0006-4971 1528-0020 |
language | eng |
recordid | cdi_crossref_primary_10_1182_blood_2018_99_111956 |
source | ScienceDirect Journals |
title | PD-L1 Expression Is Low in Large B-Cell Lymphoma with MYC or Double-Hit Translocation |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T06%3A10%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=PD-L1%20Expression%20Is%20Low%20in%20Large%20B-Cell%20Lymphoma%20with%20MYC%20or%20Double-Hit%20Translocation&rft.jtitle=Blood&rft.au=Elb%C3%A6k,%20Mette%20Vestergaard&rft.date=2018-11-29&rft.volume=132&rft.issue=Supplement%201&rft.spage=4113&rft.epage=4113&rft.pages=4113-4113&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood-2018-99-111956&rft_dat=%3Celsevier_cross%3ES0006497119402139%3C/elsevier_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c1976-28ae7dbcf1175eb168240ea1dfddc64ddd3b150427a477304bca4137fa3b2ec13%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |