HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for large B-cell lymphoma
•Low prelymphodepletion mHLA-DR correlates with older age, poorer ECOG performance status, higher tumor burden, and systemic inflammation.•Low prelymphodepletion mHLA-DR is associated with poorer duration of response and survival in LBCL treated with anti-CD19 CAR T cells. [Display omitted] Despite...
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| Veröffentlicht in: | Blood advances 2023-03, Vol.7 (5), p.744-755 |
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| creator | Bourbon, Estelle Sesques, Pierre Gossez, Morgane Tordo, Jérémie Ferrant, Emmanuelle Safar, Violaine Wallet, Florent Aussedat, Guillaume Maarek, Alizée Bouafia, Fadhela Karlin, Lionel Ghergus, Dana Golfier, Camille Lequeu, Hélène Lazareth, Anne Schwiertz, Vérane Viel, Sébastien Idlhaj, Maryam Ghesquières, Hervé Monneret, Guillaume Bachy, Emmanuel Venet, Fabienne |
| description | •Low prelymphodepletion mHLA-DR correlates with older age, poorer ECOG performance status, higher tumor burden, and systemic inflammation.•Low prelymphodepletion mHLA-DR is associated with poorer duration of response and survival in LBCL treated with anti-CD19 CAR T cells.
[Display omitted]
Despite their unprecedented success in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, and more than half of patients relapse. As monocytes emerged as key players in CAR therapy, we sought to evaluate the evolution of HLA-DR expression on monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in a large cohort (n = 103) of patients with R/R LBCL and its association with adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), the mHLA-DR level decreased after LD, and this decrease was associated with poorer outcome. Low mHLA-DR at day minus 7 (D−7) ( |
| doi_str_mv | 10.1182/bloodadvances.2021006563 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_hal_p</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9989525</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2473952922002439</els_id><sourcerecordid>35439292</sourcerecordid><originalsourceid>FETCH-LOGICAL-c516t-2580637f23bde0e52e589002eaa9ff18e8abccc4af021a2887ae415bd082f2af3</originalsourceid><addsrcrecordid>eNqFUdtq3DAQFaWlCUl-IegD6lQXy5ZeCptNmy0sBEL6LGRplFWxLSM5S_fvo-J00_SlIJCGOZfRHIQwJVeUSva562N0xu3NaCFfMcIoIY1o-Dt0yuqWV0rw9v3xzdQJusj5JyGEtg0Xin1EJ1zUXDHFTpHbbFfVzT2GX1OCnEMccTlDHKM9zJCxGR2OT7ONA-DoSzmHan1DFV6v7vFDZaHv8byDZKYD9jHh3qRHwNdLoz8M0y4O5hx98KbPcPFyn6Ef374-rDfV9u72-3q1raygzVwxIUnDW89454CAYCCkIoSBMcp7KkGazlpbG1_-bJiUrYGais4RyTwznp-hL4vu9NQN4CyMczK9nlIYTDroaIJ-2xnDTj_GvVZKlk2JIvBpEdj9Q9ustjqMGdKgSU2KtWr3tMDlArcp5pzAHzmU6N9Z6TdZ6desCvXy71GPxD_JFMD1AoCysH2ApLMNUGRcSGBn7WL4v8sz4GmrTg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for large B-cell lymphoma</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Bourbon, Estelle ; Sesques, Pierre ; Gossez, Morgane ; Tordo, Jérémie ; Ferrant, Emmanuelle ; Safar, Violaine ; Wallet, Florent ; Aussedat, Guillaume ; Maarek, Alizée ; Bouafia, Fadhela ; Karlin, Lionel ; Ghergus, Dana ; Golfier, Camille ; Lequeu, Hélène ; Lazareth, Anne ; Schwiertz, Vérane ; Viel, Sébastien ; Idlhaj, Maryam ; Ghesquières, Hervé ; Monneret, Guillaume ; Bachy, Emmanuel ; Venet, Fabienne</creator><creatorcontrib>Bourbon, Estelle ; Sesques, Pierre ; Gossez, Morgane ; Tordo, Jérémie ; Ferrant, Emmanuelle ; Safar, Violaine ; Wallet, Florent ; Aussedat, Guillaume ; Maarek, Alizée ; Bouafia, Fadhela ; Karlin, Lionel ; Ghergus, Dana ; Golfier, Camille ; Lequeu, Hélène ; Lazareth, Anne ; Schwiertz, Vérane ; Viel, Sébastien ; Idlhaj, Maryam ; Ghesquières, Hervé ; Monneret, Guillaume ; Bachy, Emmanuel ; Venet, Fabienne</creatorcontrib><description>•Low prelymphodepletion mHLA-DR correlates with older age, poorer ECOG performance status, higher tumor burden, and systemic inflammation.•Low prelymphodepletion mHLA-DR is associated with poorer duration of response and survival in LBCL treated with anti-CD19 CAR T cells.
[Display omitted]
Despite their unprecedented success in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, and more than half of patients relapse. As monocytes emerged as key players in CAR therapy, we sought to evaluate the evolution of HLA-DR expression on monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in a large cohort (n = 103) of patients with R/R LBCL and its association with adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), the mHLA-DR level decreased after LD, and this decrease was associated with poorer outcome. Low mHLA-DR at day minus 7 (D−7) (<13 500 antibodies per cell) before CAR T-cell infusion correlated with older age, poorer performance status, higher tumor burden, and elevated inflammatory markers. With a median follow-up of 7.4 months, patients with low mHLA-DR D−7 exhibited a poorer duration of response and survival than the higher mHLA-DR D−7 group. For toxicity management, tocilizumab was more frequently used in the low–mHLA-DR D−7 group. These data suggest that monocyte dysregulation before LD, characterized by the downregulation of mHLA-DR, correlates with an inflammatory and immunosuppressive tumor environment and is associated with failure of anti-CD19 CAR T cells in patients with R/R LBCL. Modulation of these myeloid cells represents a promising field for improving CAR therapy.</description><identifier>ISSN: 2473-9529</identifier><identifier>EISSN: 2473-9537</identifier><identifier>DOI: 10.1182/bloodadvances.2021006563</identifier><identifier>PMID: 35439292</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>HLA-DR Antigens ; Humans ; Immunobiology and Immunotherapy ; Immunotherapy, Adoptive - adverse effects ; Life Sciences ; Lymphoma, Large B-Cell, Diffuse - therapy ; Monocytes ; Neoplasm Recurrence, Local</subject><ispartof>Blood advances, 2023-03, Vol.7 (5), p.744-755</ispartof><rights>2023 The American Society of Hematology</rights><rights>2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. 2023 The American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c516t-2580637f23bde0e52e589002eaa9ff18e8abccc4af021a2887ae415bd082f2af3</citedby><cites>FETCH-LOGICAL-c516t-2580637f23bde0e52e589002eaa9ff18e8abccc4af021a2887ae415bd082f2af3</cites><orcidid>0000-0002-6521-8815 ; 0000-0003-2694-7510 ; 0000-0003-1930-8956 ; 0000-0003-3174-6246 ; 0000-0003-4934-283X ; 0000-0003-0462-4235 ; 0000-0002-9961-5739 ; 0000-0002-5085-443X ; 0000-0001-8264-822X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989525/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989525/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35439292$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-04028897$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Bourbon, Estelle</creatorcontrib><creatorcontrib>Sesques, Pierre</creatorcontrib><creatorcontrib>Gossez, Morgane</creatorcontrib><creatorcontrib>Tordo, Jérémie</creatorcontrib><creatorcontrib>Ferrant, Emmanuelle</creatorcontrib><creatorcontrib>Safar, Violaine</creatorcontrib><creatorcontrib>Wallet, Florent</creatorcontrib><creatorcontrib>Aussedat, Guillaume</creatorcontrib><creatorcontrib>Maarek, Alizée</creatorcontrib><creatorcontrib>Bouafia, Fadhela</creatorcontrib><creatorcontrib>Karlin, Lionel</creatorcontrib><creatorcontrib>Ghergus, Dana</creatorcontrib><creatorcontrib>Golfier, Camille</creatorcontrib><creatorcontrib>Lequeu, Hélène</creatorcontrib><creatorcontrib>Lazareth, Anne</creatorcontrib><creatorcontrib>Schwiertz, Vérane</creatorcontrib><creatorcontrib>Viel, Sébastien</creatorcontrib><creatorcontrib>Idlhaj, Maryam</creatorcontrib><creatorcontrib>Ghesquières, Hervé</creatorcontrib><creatorcontrib>Monneret, Guillaume</creatorcontrib><creatorcontrib>Bachy, Emmanuel</creatorcontrib><creatorcontrib>Venet, Fabienne</creatorcontrib><title>HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for large B-cell lymphoma</title><title>Blood advances</title><addtitle>Blood Adv</addtitle><description>•Low prelymphodepletion mHLA-DR correlates with older age, poorer ECOG performance status, higher tumor burden, and systemic inflammation.•Low prelymphodepletion mHLA-DR is associated with poorer duration of response and survival in LBCL treated with anti-CD19 CAR T cells.
[Display omitted]
Despite their unprecedented success in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, and more than half of patients relapse. As monocytes emerged as key players in CAR therapy, we sought to evaluate the evolution of HLA-DR expression on monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in a large cohort (n = 103) of patients with R/R LBCL and its association with adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), the mHLA-DR level decreased after LD, and this decrease was associated with poorer outcome. Low mHLA-DR at day minus 7 (D−7) (<13 500 antibodies per cell) before CAR T-cell infusion correlated with older age, poorer performance status, higher tumor burden, and elevated inflammatory markers. With a median follow-up of 7.4 months, patients with low mHLA-DR D−7 exhibited a poorer duration of response and survival than the higher mHLA-DR D−7 group. For toxicity management, tocilizumab was more frequently used in the low–mHLA-DR D−7 group. These data suggest that monocyte dysregulation before LD, characterized by the downregulation of mHLA-DR, correlates with an inflammatory and immunosuppressive tumor environment and is associated with failure of anti-CD19 CAR T cells in patients with R/R LBCL. Modulation of these myeloid cells represents a promising field for improving CAR therapy.</description><subject>HLA-DR Antigens</subject><subject>Humans</subject><subject>Immunobiology and Immunotherapy</subject><subject>Immunotherapy, Adoptive - adverse effects</subject><subject>Life Sciences</subject><subject>Lymphoma, Large B-Cell, Diffuse - therapy</subject><subject>Monocytes</subject><subject>Neoplasm Recurrence, Local</subject><issn>2473-9529</issn><issn>2473-9537</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUdtq3DAQFaWlCUl-IegD6lQXy5ZeCptNmy0sBEL6LGRplFWxLSM5S_fvo-J00_SlIJCGOZfRHIQwJVeUSva562N0xu3NaCFfMcIoIY1o-Dt0yuqWV0rw9v3xzdQJusj5JyGEtg0Xin1EJ1zUXDHFTpHbbFfVzT2GX1OCnEMccTlDHKM9zJCxGR2OT7ONA-DoSzmHan1DFV6v7vFDZaHv8byDZKYD9jHh3qRHwNdLoz8M0y4O5hx98KbPcPFyn6Ef374-rDfV9u72-3q1raygzVwxIUnDW89454CAYCCkIoSBMcp7KkGazlpbG1_-bJiUrYGais4RyTwznp-hL4vu9NQN4CyMczK9nlIYTDroaIJ-2xnDTj_GvVZKlk2JIvBpEdj9Q9ustjqMGdKgSU2KtWr3tMDlArcp5pzAHzmU6N9Z6TdZ6desCvXy71GPxD_JFMD1AoCysH2ApLMNUGRcSGBn7WL4v8sz4GmrTg</recordid><startdate>20230314</startdate><enddate>20230314</enddate><creator>Bourbon, Estelle</creator><creator>Sesques, Pierre</creator><creator>Gossez, Morgane</creator><creator>Tordo, Jérémie</creator><creator>Ferrant, Emmanuelle</creator><creator>Safar, Violaine</creator><creator>Wallet, Florent</creator><creator>Aussedat, Guillaume</creator><creator>Maarek, Alizée</creator><creator>Bouafia, Fadhela</creator><creator>Karlin, Lionel</creator><creator>Ghergus, Dana</creator><creator>Golfier, Camille</creator><creator>Lequeu, Hélène</creator><creator>Lazareth, Anne</creator><creator>Schwiertz, Vérane</creator><creator>Viel, Sébastien</creator><creator>Idlhaj, Maryam</creator><creator>Ghesquières, Hervé</creator><creator>Monneret, Guillaume</creator><creator>Bachy, Emmanuel</creator><creator>Venet, Fabienne</creator><general>Elsevier Inc</general><general>The American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</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>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6521-8815</orcidid><orcidid>https://orcid.org/0000-0003-2694-7510</orcidid><orcidid>https://orcid.org/0000-0003-1930-8956</orcidid><orcidid>https://orcid.org/0000-0003-3174-6246</orcidid><orcidid>https://orcid.org/0000-0003-4934-283X</orcidid><orcidid>https://orcid.org/0000-0003-0462-4235</orcidid><orcidid>https://orcid.org/0000-0002-9961-5739</orcidid><orcidid>https://orcid.org/0000-0002-5085-443X</orcidid><orcidid>https://orcid.org/0000-0001-8264-822X</orcidid></search><sort><creationdate>20230314</creationdate><title>HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for large B-cell lymphoma</title><author>Bourbon, Estelle ; 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[Display omitted]
Despite their unprecedented success in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, and more than half of patients relapse. As monocytes emerged as key players in CAR therapy, we sought to evaluate the evolution of HLA-DR expression on monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in a large cohort (n = 103) of patients with R/R LBCL and its association with adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), the mHLA-DR level decreased after LD, and this decrease was associated with poorer outcome. Low mHLA-DR at day minus 7 (D−7) (<13 500 antibodies per cell) before CAR T-cell infusion correlated with older age, poorer performance status, higher tumor burden, and elevated inflammatory markers. With a median follow-up of 7.4 months, patients with low mHLA-DR D−7 exhibited a poorer duration of response and survival than the higher mHLA-DR D−7 group. For toxicity management, tocilizumab was more frequently used in the low–mHLA-DR D−7 group. These data suggest that monocyte dysregulation before LD, characterized by the downregulation of mHLA-DR, correlates with an inflammatory and immunosuppressive tumor environment and is associated with failure of anti-CD19 CAR T cells in patients with R/R LBCL. Modulation of these myeloid cells represents a promising field for improving CAR therapy.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35439292</pmid><doi>10.1182/bloodadvances.2021006563</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-6521-8815</orcidid><orcidid>https://orcid.org/0000-0003-2694-7510</orcidid><orcidid>https://orcid.org/0000-0003-1930-8956</orcidid><orcidid>https://orcid.org/0000-0003-3174-6246</orcidid><orcidid>https://orcid.org/0000-0003-4934-283X</orcidid><orcidid>https://orcid.org/0000-0003-0462-4235</orcidid><orcidid>https://orcid.org/0000-0002-9961-5739</orcidid><orcidid>https://orcid.org/0000-0002-5085-443X</orcidid><orcidid>https://orcid.org/0000-0001-8264-822X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | HLA-DR Antigens Humans Immunobiology and Immunotherapy Immunotherapy, Adoptive - adverse effects Life Sciences Lymphoma, Large B-Cell, Diffuse - therapy Monocytes Neoplasm Recurrence, Local |
| title | HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for large B-cell lymphoma |
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