Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent
Previous studies have suggested a negative impact of steroids on the efficacy of immune checkpoint inhibitors (ICI), but how this effect is modulated by the dosage and time of administration is yet to be clarified. We have performed a retrospective analysis of 475 patients with advanced solid tumors...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy : CII Immunotherapy : CII, 2024-08, Vol.73 (10), p.186, Article 186 |
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| creator | Albarrán, Víctor Guerrero, Patricia de Quevedo, Coral García González, Carlos Chamorro, Jesús Rosero, Diana Isabel Moreno, Jaime Calvo, Juan Carlos de Aguado, Patricia Pérez Alía, Víctor Sotoca, Pilar Barrill, Ana María Román, María San Álvarez-Ballesteros, Pablo Serrano, Juan José Soria, Ainara Olmedo, María Eugenia Saavedra, Cristina Cortés, Alfonso Gómez, Ana Lage, Yolanda Ruiz, Álvaro Ferreiro, María Reyes Longo, Federico Garrido, Pilar Gajate, Pablo |
| description | Previous studies have suggested a negative impact of steroids on the efficacy of immune checkpoint inhibitors (ICI), but how this effect is modulated by the dosage and time of administration is yet to be clarified. We have performed a retrospective analysis of 475 patients with advanced solid tumors treated with ICI as monotherapy from 2015 to 2022. Data regarding immune-related adverse events (irAEs) and clinical outcomes were collected. For each patient, the daily steroid dose (in mg/kg of prednisone) was registered until disease progression or death. The impact of cumulative doses on response rates and survival outcomes was analyzed within different periods. The objective response rate (ORR) was significantly lower among patients exposed to steroids within 30 days before the first cycle of ICI (C1) (20.3% vs. 36.7%,
p
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| doi_str_mv | 10.1007/s00262-024-03772-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11297225</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3087428747</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-ca0191ad20abd488e0324d56e80367e7d5e702b7b1d1289caf1fae966bb3d54b3</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhiNERUvhD3BAlrhwCR3bSRxzQajiS6rgAmfLsSe7rmJ7sZ2i_feYbiltDxxGM_I8845Hb9O8oPCGAoizDMAG1gLrWuBCsFY-ak5ox-vT2NPHd-rj5mnOlwAdAymfNMdcguRcjCeN_4obXdwVEp1zNK7WMZA4k1wwRWcz-eXKljjv1xDLFpPe7QnOszPa7IkLRBO_LsW1ZfUxERO3MZW3pDhfFYMlNmZsLe4wWAzlWXM06yXj85t82vz4-OH7-ef24tunL-fvL1rD-6G0RgOVVFsGerLdOCJw1tl-wBH4IFDYHgWwSUzUUjZKo2c6a5TDME3c9t3ET5t3B93dOnm0pq5OelG75LxOexW1U_c7wW3VJl4pSpkUjPVV4fWNQoo_V8xFeZcNLosOGNesOIyC9z0MQ0VfPUAv45pCve-a6lgNUSl2oEyKOSecb39DQf2xUx3sVNVOdW2nknXo5d07bkf--lcBfgBybYUNpn-7_yP7G1xKrWM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3087428747</pqid></control><display><type>article</type><title>Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Springer Nature OA Free Journals</source><creator>Albarrán, Víctor ; Guerrero, Patricia ; de Quevedo, Coral García ; González, Carlos ; Chamorro, Jesús ; Rosero, Diana Isabel ; Moreno, Jaime ; Calvo, Juan Carlos ; de Aguado, Patricia Pérez ; Alía, Víctor ; Sotoca, Pilar ; Barrill, Ana María ; Román, María San ; Álvarez-Ballesteros, Pablo ; Serrano, Juan José ; Soria, Ainara ; Olmedo, María Eugenia ; Saavedra, Cristina ; Cortés, Alfonso ; Gómez, Ana ; Lage, Yolanda ; Ruiz, Álvaro ; Ferreiro, María Reyes ; Longo, Federico ; Garrido, Pilar ; Gajate, Pablo</creator><creatorcontrib>Albarrán, Víctor ; Guerrero, Patricia ; de Quevedo, Coral García ; González, Carlos ; Chamorro, Jesús ; Rosero, Diana Isabel ; Moreno, Jaime ; Calvo, Juan Carlos ; de Aguado, Patricia Pérez ; Alía, Víctor ; Sotoca, Pilar ; Barrill, Ana María ; Román, María San ; Álvarez-Ballesteros, Pablo ; Serrano, Juan José ; Soria, Ainara ; Olmedo, María Eugenia ; Saavedra, Cristina ; Cortés, Alfonso ; Gómez, Ana ; Lage, Yolanda ; Ruiz, Álvaro ; Ferreiro, María Reyes ; Longo, Federico ; Garrido, Pilar ; Gajate, Pablo</creatorcontrib><description>Previous studies have suggested a negative impact of steroids on the efficacy of immune checkpoint inhibitors (ICI), but how this effect is modulated by the dosage and time of administration is yet to be clarified. We have performed a retrospective analysis of 475 patients with advanced solid tumors treated with ICI as monotherapy from 2015 to 2022. Data regarding immune-related adverse events (irAEs) and clinical outcomes were collected. For each patient, the daily steroid dose (in mg/kg of prednisone) was registered until disease progression or death. The impact of cumulative doses on response rates and survival outcomes was analyzed within different periods. The objective response rate (ORR) was significantly lower among patients exposed to steroids within 30 days before the first cycle of ICI (C1) (20.3% vs. 36.7%,
p
< 0.01) and within the first 90 days of treatment (25.7% vs. 37.7%,
p
= 0.01). This negative association was confirmed by multivariable analysis. Higher mean steroid doses were observed among non-responders, and cumulative doses were inversely correlated with the disease control rate (DCR) around ICI initiation. Remarkably, poorer outcomes were observed even in patients belonging to the lowest dose quartile compared to the steroid-naïve population. The exposure to steroids after 6 months of ICI was not associated with worse survival outcomes. Our results suggest that the potential impact of steroids on ICI efficacy may be time-dependent, prevailing around ICI initiation, and dose-dependent, with modulation of neutrophil-to-lymphocyte ratio as a possible underlying mechanism.</description><identifier>ISSN: 1432-0851</identifier><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-024-03772-9</identifier><identifier>PMID: 39093378</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Cancer Research ; Disease control ; Dose-Response Relationship, Drug ; Female ; Humans ; Immune checkpoint inhibitors ; Immune Checkpoint Inhibitors - adverse effects ; Immune Checkpoint Inhibitors - therapeutic use ; Immunology ; Immunotherapy ; Immunotherapy - methods ; Leukocytes (neutrophilic) ; Lymphocytes ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Neoplasms - drug therapy ; Neoplasms - immunology ; Neoplasms - mortality ; Oncology ; Patients ; Prednisone ; Retrospective Studies ; Solid tumors ; Steroid hormones ; Steroids ; Steroids - administration & dosage ; Steroids - therapeutic use ; Time Factors</subject><ispartof>Cancer Immunology, Immunotherapy : CII, 2024-08, Vol.73 (10), p.186, Article 186</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-ca0191ad20abd488e0324d56e80367e7d5e702b7b1d1289caf1fae966bb3d54b3</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/PMC11297225/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297225/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41096,41464,42165,42533,51294,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39093378$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Albarrán, Víctor</creatorcontrib><creatorcontrib>Guerrero, Patricia</creatorcontrib><creatorcontrib>de Quevedo, Coral García</creatorcontrib><creatorcontrib>González, Carlos</creatorcontrib><creatorcontrib>Chamorro, Jesús</creatorcontrib><creatorcontrib>Rosero, Diana Isabel</creatorcontrib><creatorcontrib>Moreno, Jaime</creatorcontrib><creatorcontrib>Calvo, Juan Carlos</creatorcontrib><creatorcontrib>de Aguado, Patricia Pérez</creatorcontrib><creatorcontrib>Alía, Víctor</creatorcontrib><creatorcontrib>Sotoca, Pilar</creatorcontrib><creatorcontrib>Barrill, Ana María</creatorcontrib><creatorcontrib>Román, María San</creatorcontrib><creatorcontrib>Álvarez-Ballesteros, Pablo</creatorcontrib><creatorcontrib>Serrano, Juan José</creatorcontrib><creatorcontrib>Soria, Ainara</creatorcontrib><creatorcontrib>Olmedo, María Eugenia</creatorcontrib><creatorcontrib>Saavedra, Cristina</creatorcontrib><creatorcontrib>Cortés, Alfonso</creatorcontrib><creatorcontrib>Gómez, Ana</creatorcontrib><creatorcontrib>Lage, Yolanda</creatorcontrib><creatorcontrib>Ruiz, Álvaro</creatorcontrib><creatorcontrib>Ferreiro, María Reyes</creatorcontrib><creatorcontrib>Longo, Federico</creatorcontrib><creatorcontrib>Garrido, Pilar</creatorcontrib><creatorcontrib>Gajate, Pablo</creatorcontrib><title>Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent</title><title>Cancer Immunology, Immunotherapy : CII</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Previous studies have suggested a negative impact of steroids on the efficacy of immune checkpoint inhibitors (ICI), but how this effect is modulated by the dosage and time of administration is yet to be clarified. We have performed a retrospective analysis of 475 patients with advanced solid tumors treated with ICI as monotherapy from 2015 to 2022. Data regarding immune-related adverse events (irAEs) and clinical outcomes were collected. For each patient, the daily steroid dose (in mg/kg of prednisone) was registered until disease progression or death. The impact of cumulative doses on response rates and survival outcomes was analyzed within different periods. The objective response rate (ORR) was significantly lower among patients exposed to steroids within 30 days before the first cycle of ICI (C1) (20.3% vs. 36.7%,
p
< 0.01) and within the first 90 days of treatment (25.7% vs. 37.7%,
p
= 0.01). This negative association was confirmed by multivariable analysis. Higher mean steroid doses were observed among non-responders, and cumulative doses were inversely correlated with the disease control rate (DCR) around ICI initiation. Remarkably, poorer outcomes were observed even in patients belonging to the lowest dose quartile compared to the steroid-naïve population. The exposure to steroids after 6 months of ICI was not associated with worse survival outcomes. Our results suggest that the potential impact of steroids on ICI efficacy may be time-dependent, prevailing around ICI initiation, and dose-dependent, with modulation of neutrophil-to-lymphocyte ratio as a possible underlying mechanism.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cancer Research</subject><subject>Disease control</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Humans</subject><subject>Immune checkpoint inhibitors</subject><subject>Immune Checkpoint Inhibitors - adverse effects</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - mortality</subject><subject>Oncology</subject><subject>Patients</subject><subject>Prednisone</subject><subject>Retrospective Studies</subject><subject>Solid tumors</subject><subject>Steroid hormones</subject><subject>Steroids</subject><subject>Steroids - administration & dosage</subject><subject>Steroids - therapeutic use</subject><subject>Time Factors</subject><issn>1432-0851</issn><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhiNERUvhD3BAlrhwCR3bSRxzQajiS6rgAmfLsSe7rmJ7sZ2i_feYbiltDxxGM_I8845Hb9O8oPCGAoizDMAG1gLrWuBCsFY-ak5ox-vT2NPHd-rj5mnOlwAdAymfNMdcguRcjCeN_4obXdwVEp1zNK7WMZA4k1wwRWcz-eXKljjv1xDLFpPe7QnOszPa7IkLRBO_LsW1ZfUxERO3MZW3pDhfFYMlNmZsLe4wWAzlWXM06yXj85t82vz4-OH7-ef24tunL-fvL1rD-6G0RgOVVFsGerLdOCJw1tl-wBH4IFDYHgWwSUzUUjZKo2c6a5TDME3c9t3ET5t3B93dOnm0pq5OelG75LxOexW1U_c7wW3VJl4pSpkUjPVV4fWNQoo_V8xFeZcNLosOGNesOIyC9z0MQ0VfPUAv45pCve-a6lgNUSl2oEyKOSecb39DQf2xUx3sVNVOdW2nknXo5d07bkf--lcBfgBybYUNpn-7_yP7G1xKrWM</recordid><startdate>20240802</startdate><enddate>20240802</enddate><creator>Albarrán, Víctor</creator><creator>Guerrero, Patricia</creator><creator>de Quevedo, Coral García</creator><creator>González, Carlos</creator><creator>Chamorro, Jesús</creator><creator>Rosero, Diana Isabel</creator><creator>Moreno, Jaime</creator><creator>Calvo, Juan Carlos</creator><creator>de Aguado, Patricia Pérez</creator><creator>Alía, Víctor</creator><creator>Sotoca, Pilar</creator><creator>Barrill, Ana María</creator><creator>Román, María San</creator><creator>Álvarez-Ballesteros, Pablo</creator><creator>Serrano, Juan José</creator><creator>Soria, Ainara</creator><creator>Olmedo, María Eugenia</creator><creator>Saavedra, Cristina</creator><creator>Cortés, Alfonso</creator><creator>Gómez, Ana</creator><creator>Lage, Yolanda</creator><creator>Ruiz, Álvaro</creator><creator>Ferreiro, María Reyes</creator><creator>Longo, Federico</creator><creator>Garrido, Pilar</creator><creator>Gajate, Pablo</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</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>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20240802</creationdate><title>Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent</title><author>Albarrán, Víctor ; Guerrero, Patricia ; de Quevedo, Coral García ; González, Carlos ; Chamorro, Jesús ; Rosero, Diana Isabel ; Moreno, Jaime ; Calvo, Juan Carlos ; de Aguado, Patricia Pérez ; Alía, Víctor ; Sotoca, Pilar ; Barrill, Ana María ; Román, María San ; Álvarez-Ballesteros, Pablo ; Serrano, Juan José ; Soria, Ainara ; Olmedo, María Eugenia ; Saavedra, Cristina ; Cortés, Alfonso ; Gómez, Ana ; Lage, Yolanda ; Ruiz, Álvaro ; Ferreiro, María Reyes ; Longo, Federico ; Garrido, Pilar ; Gajate, Pablo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-ca0191ad20abd488e0324d56e80367e7d5e702b7b1d1289caf1fae966bb3d54b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cancer Research</topic><topic>Disease control</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Humans</topic><topic>Immune checkpoint inhibitors</topic><topic>Immune Checkpoint Inhibitors - 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We have performed a retrospective analysis of 475 patients with advanced solid tumors treated with ICI as monotherapy from 2015 to 2022. Data regarding immune-related adverse events (irAEs) and clinical outcomes were collected. For each patient, the daily steroid dose (in mg/kg of prednisone) was registered until disease progression or death. The impact of cumulative doses on response rates and survival outcomes was analyzed within different periods. The objective response rate (ORR) was significantly lower among patients exposed to steroids within 30 days before the first cycle of ICI (C1) (20.3% vs. 36.7%,
p
< 0.01) and within the first 90 days of treatment (25.7% vs. 37.7%,
p
= 0.01). This negative association was confirmed by multivariable analysis. Higher mean steroid doses were observed among non-responders, and cumulative doses were inversely correlated with the disease control rate (DCR) around ICI initiation. Remarkably, poorer outcomes were observed even in patients belonging to the lowest dose quartile compared to the steroid-naïve population. The exposure to steroids after 6 months of ICI was not associated with worse survival outcomes. Our results suggest that the potential impact of steroids on ICI efficacy may be time-dependent, prevailing around ICI initiation, and dose-dependent, with modulation of neutrophil-to-lymphocyte ratio as a possible underlying mechanism.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>39093378</pmid><doi>10.1007/s00262-024-03772-9</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer Immunology, Immunotherapy : CII, 2024-08, Vol.73 (10), p.186, Article 186 |
| issn | 1432-0851 0340-7004 1432-0851 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals; PubMed Central; Alma/SFX Local Collection; Springer Nature OA Free Journals |
| subjects | Adult Aged Aged, 80 and over Cancer Research Disease control Dose-Response Relationship, Drug Female Humans Immune checkpoint inhibitors Immune Checkpoint Inhibitors - adverse effects Immune Checkpoint Inhibitors - therapeutic use Immunology Immunotherapy Immunotherapy - methods Leukocytes (neutrophilic) Lymphocytes Male Medicine Medicine & Public Health Middle Aged Neoplasms - drug therapy Neoplasms - immunology Neoplasms - mortality Oncology Patients Prednisone Retrospective Studies Solid tumors Steroid hormones Steroids Steroids - administration & dosage Steroids - therapeutic use Time Factors |
| title | Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent |
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