Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma
Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus...
Gespeichert in:
| Veröffentlicht in: | EUROPEAN JOURNAL OF CANCER 2024-08, Vol.207, p.114172, Article 114172 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | |
| container_start_page | 114172 |
| container_title | EUROPEAN JOURNAL OF CANCER |
| container_volume | 207 |
| creator | Verheijden, Rik J. Burgers, Femke H. Janssen, Josephine C. Putker, Anouk E. Veenstra, Sophie P.G.R. Hospers, Geke A.P. Aarts, Maureen J.B. Hehenkamp, Karel W. Doornebosch, Veerle L.E. Verhaert, Marthe van den Berkmortel, Franchette W.P.J. Chatzidionysiou, Katerina Llobell, Arturo Barros, Milton Maria, Alexandre T.J. Takeji, Akari García Morillo, José-Salvador Lidar, Merav van Eijs, Mick J.M. Blank, Christian U. Aspeslagh, Sandrine Piersma, Djura Kapiteijn, Ellen Labots, Mariette Boers-Sonderen, Marye J. van der Veldt, Astrid A.M. Haanen, John B.A.G. May, Anne M. Suijkerbuijk, Karijn P.M. |
| description | Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs.
Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression.
Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4–8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4–14) and 55 (95 %CI 41–not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HRadj 1.14; 95 %CI 1.01–1.29; HRadj 1.29; 95 %CI 1.12–1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02–1.72) and OS (HRadj 1.34; 95 %CI 0.99–1.82) compared with corticosteroids alone.
High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.
irAE guidelines advise starting with 1-2 mg/kg prednisone for most ≥grade 3 irAEs.Previous papers suggest that immunosuppression for irAEs impairs survival.Whether this is due to steroid dose or second-line immunosuppression is unknown.We show that both steroid peak dose and second-line immunosuppression are associated with survival.This suggest that it may be better to start with lower steroid doses whenever possible. |
| doi_str_mv | 10.1016/j.ejca.2024.114172 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_proquest_miscellaneous_3071085978</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0959804924008281</els_id><sourcerecordid>3071085978</sourcerecordid><originalsourceid>FETCH-LOGICAL-c319t-9b7ca5c649c8297980e9542c7c444836c0c6fc7612d1ebef6576ef912d3fcf663</originalsourceid><addsrcrecordid>eNp9kTuP1DAUhS0EYmcX_gAFSkmTwU4cPyQaNOKx0ko0UFvOzbXGs5M42M4gSv45jjJsSWX76DvnWvcQ8obRPaNMvD_t8QR239CG7xnjTDbPyI4pqWuquuY52VHd6VpRrm_IbUonSqlUnL4kN63StFNM7cifQ4jZQ0gZY_BDquw0VCEfMVZ-HJcppGWeI6Zkp5wqF64y1hHPNuNQ2eGCMWGFF1yJ1Q5HhMc5-ClXfjr63udiQ-cQsi9UCSt6NZaAKYz2FXnh7Dnh6-t5R358_vT98LV--Pbl_vDxoYaW6VzrXoLtQHANqtFSK4q64w1I4JyrVgAF4UAK1gwMe3SikwKdLs_WgROivSP1lpt-4bz0Zo5-tPG3Cdabq_RYbmiULgNX_t3GzzH8XDBlM_oEeC6_xrAk01LJyp61VAVtNhRiSCmiewpn1KxVmZNZqzJrVWarqpjeXvOXfsThyfKvmwJ82AAsW7l4jCaBxwlw8LGs0gzB_y__L0B1qR4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3071085978</pqid></control><display><type>article</type><title>Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Verheijden, Rik J. ; Burgers, Femke H. ; Janssen, Josephine C. ; Putker, Anouk E. ; Veenstra, Sophie P.G.R. ; Hospers, Geke A.P. ; Aarts, Maureen J.B. ; Hehenkamp, Karel W. ; Doornebosch, Veerle L.E. ; Verhaert, Marthe ; van den Berkmortel, Franchette W.P.J. ; Chatzidionysiou, Katerina ; Llobell, Arturo ; Barros, Milton ; Maria, Alexandre T.J. ; Takeji, Akari ; García Morillo, José-Salvador ; Lidar, Merav ; van Eijs, Mick J.M. ; Blank, Christian U. ; Aspeslagh, Sandrine ; Piersma, Djura ; Kapiteijn, Ellen ; Labots, Mariette ; Boers-Sonderen, Marye J. ; van der Veldt, Astrid A.M. ; Haanen, John B.A.G. ; May, Anne M. ; Suijkerbuijk, Karijn P.M.</creator><creatorcontrib>Verheijden, Rik J. ; Burgers, Femke H. ; Janssen, Josephine C. ; Putker, Anouk E. ; Veenstra, Sophie P.G.R. ; Hospers, Geke A.P. ; Aarts, Maureen J.B. ; Hehenkamp, Karel W. ; Doornebosch, Veerle L.E. ; Verhaert, Marthe ; van den Berkmortel, Franchette W.P.J. ; Chatzidionysiou, Katerina ; Llobell, Arturo ; Barros, Milton ; Maria, Alexandre T.J. ; Takeji, Akari ; García Morillo, José-Salvador ; Lidar, Merav ; van Eijs, Mick J.M. ; Blank, Christian U. ; Aspeslagh, Sandrine ; Piersma, Djura ; Kapiteijn, Ellen ; Labots, Mariette ; Boers-Sonderen, Marye J. ; van der Veldt, Astrid A.M. ; Haanen, John B.A.G. ; May, Anne M. ; Suijkerbuijk, Karijn P.M.</creatorcontrib><description>Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs.
Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression.
Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4–8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4–14) and 55 (95 %CI 41–not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HRadj 1.14; 95 %CI 1.01–1.29; HRadj 1.29; 95 %CI 1.12–1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02–1.72) and OS (HRadj 1.34; 95 %CI 0.99–1.82) compared with corticosteroids alone.
High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.
irAE guidelines advise starting with 1-2 mg/kg prednisone for most ≥grade 3 irAEs.Previous papers suggest that immunosuppression for irAEs impairs survival.Whether this is due to steroid dose or second-line immunosuppression is unknown.We show that both steroid peak dose and second-line immunosuppression are associated with survival.This suggest that it may be better to start with lower steroid doses whenever possible.</description><identifier>ISSN: 0959-8049</identifier><identifier>ISSN: 1879-0852</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2024.114172</identifier><identifier>PMID: 38905818</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adrenal Cortex Hormones - adverse effects ; Adrenal Cortex Hormones - therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Checkpoint inhibitor ; Corticosteroids ; Female ; Humans ; Immune Checkpoint Inhibitors - adverse effects ; Immune-related adverse events ; Immunosuppression ; Immunosuppressive Agents - adverse effects ; Immunosuppressive Agents - therapeutic use ; Male ; Melanoma ; Melanoma - drug therapy ; Melanoma - immunology ; Melanoma - mortality ; Middle Aged ; Retrospective Studies ; Skin Neoplasms - drug therapy ; Skin Neoplasms - immunology ; Skin Neoplasms - mortality ; Toxicity</subject><ispartof>EUROPEAN JOURNAL OF CANCER, 2024-08, Vol.207, p.114172, Article 114172</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c319t-9b7ca5c649c8297980e9542c7c444836c0c6fc7612d1ebef6576ef912d3fcf663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejca.2024.114172$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38905818$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:159783325$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Verheijden, Rik J.</creatorcontrib><creatorcontrib>Burgers, Femke H.</creatorcontrib><creatorcontrib>Janssen, Josephine C.</creatorcontrib><creatorcontrib>Putker, Anouk E.</creatorcontrib><creatorcontrib>Veenstra, Sophie P.G.R.</creatorcontrib><creatorcontrib>Hospers, Geke A.P.</creatorcontrib><creatorcontrib>Aarts, Maureen J.B.</creatorcontrib><creatorcontrib>Hehenkamp, Karel W.</creatorcontrib><creatorcontrib>Doornebosch, Veerle L.E.</creatorcontrib><creatorcontrib>Verhaert, Marthe</creatorcontrib><creatorcontrib>van den Berkmortel, Franchette W.P.J.</creatorcontrib><creatorcontrib>Chatzidionysiou, Katerina</creatorcontrib><creatorcontrib>Llobell, Arturo</creatorcontrib><creatorcontrib>Barros, Milton</creatorcontrib><creatorcontrib>Maria, Alexandre T.J.</creatorcontrib><creatorcontrib>Takeji, Akari</creatorcontrib><creatorcontrib>García Morillo, José-Salvador</creatorcontrib><creatorcontrib>Lidar, Merav</creatorcontrib><creatorcontrib>van Eijs, Mick J.M.</creatorcontrib><creatorcontrib>Blank, Christian U.</creatorcontrib><creatorcontrib>Aspeslagh, Sandrine</creatorcontrib><creatorcontrib>Piersma, Djura</creatorcontrib><creatorcontrib>Kapiteijn, Ellen</creatorcontrib><creatorcontrib>Labots, Mariette</creatorcontrib><creatorcontrib>Boers-Sonderen, Marye J.</creatorcontrib><creatorcontrib>van der Veldt, Astrid A.M.</creatorcontrib><creatorcontrib>Haanen, John B.A.G.</creatorcontrib><creatorcontrib>May, Anne M.</creatorcontrib><creatorcontrib>Suijkerbuijk, Karijn P.M.</creatorcontrib><title>Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma</title><title>EUROPEAN JOURNAL OF CANCER</title><addtitle>Eur J Cancer</addtitle><description>Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs.
Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression.
Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4–8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4–14) and 55 (95 %CI 41–not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HRadj 1.14; 95 %CI 1.01–1.29; HRadj 1.29; 95 %CI 1.12–1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02–1.72) and OS (HRadj 1.34; 95 %CI 0.99–1.82) compared with corticosteroids alone.
High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.
irAE guidelines advise starting with 1-2 mg/kg prednisone for most ≥grade 3 irAEs.Previous papers suggest that immunosuppression for irAEs impairs survival.Whether this is due to steroid dose or second-line immunosuppression is unknown.We show that both steroid peak dose and second-line immunosuppression are associated with survival.This suggest that it may be better to start with lower steroid doses whenever possible.</description><subject>Adrenal Cortex Hormones - adverse effects</subject><subject>Adrenal Cortex Hormones - therapeutic use</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Checkpoint inhibitor</subject><subject>Corticosteroids</subject><subject>Female</subject><subject>Humans</subject><subject>Immune Checkpoint Inhibitors - adverse effects</subject><subject>Immune-related adverse events</subject><subject>Immunosuppression</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Male</subject><subject>Melanoma</subject><subject>Melanoma - drug therapy</subject><subject>Melanoma - immunology</subject><subject>Melanoma - mortality</subject><subject>Middle Aged</subject><subject>Retrospective Studies</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Skin Neoplasms - immunology</subject><subject>Skin Neoplasms - mortality</subject><subject>Toxicity</subject><issn>0959-8049</issn><issn>1879-0852</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kTuP1DAUhS0EYmcX_gAFSkmTwU4cPyQaNOKx0ko0UFvOzbXGs5M42M4gSv45jjJsSWX76DvnWvcQ8obRPaNMvD_t8QR239CG7xnjTDbPyI4pqWuquuY52VHd6VpRrm_IbUonSqlUnL4kN63StFNM7cifQ4jZQ0gZY_BDquw0VCEfMVZ-HJcppGWeI6Zkp5wqF64y1hHPNuNQ2eGCMWGFF1yJ1Q5HhMc5-ClXfjr63udiQ-cQsi9UCSt6NZaAKYz2FXnh7Dnh6-t5R358_vT98LV--Pbl_vDxoYaW6VzrXoLtQHANqtFSK4q64w1I4JyrVgAF4UAK1gwMe3SikwKdLs_WgROivSP1lpt-4bz0Zo5-tPG3Cdabq_RYbmiULgNX_t3GzzH8XDBlM_oEeC6_xrAk01LJyp61VAVtNhRiSCmiewpn1KxVmZNZqzJrVWarqpjeXvOXfsThyfKvmwJ82AAsW7l4jCaBxwlw8LGs0gzB_y__L0B1qR4</recordid><startdate>20240801</startdate><enddate>20240801</enddate><creator>Verheijden, Rik J.</creator><creator>Burgers, Femke H.</creator><creator>Janssen, Josephine C.</creator><creator>Putker, Anouk E.</creator><creator>Veenstra, Sophie P.G.R.</creator><creator>Hospers, Geke A.P.</creator><creator>Aarts, Maureen J.B.</creator><creator>Hehenkamp, Karel W.</creator><creator>Doornebosch, Veerle L.E.</creator><creator>Verhaert, Marthe</creator><creator>van den Berkmortel, Franchette W.P.J.</creator><creator>Chatzidionysiou, Katerina</creator><creator>Llobell, Arturo</creator><creator>Barros, Milton</creator><creator>Maria, Alexandre T.J.</creator><creator>Takeji, Akari</creator><creator>García Morillo, José-Salvador</creator><creator>Lidar, Merav</creator><creator>van Eijs, Mick J.M.</creator><creator>Blank, Christian U.</creator><creator>Aspeslagh, Sandrine</creator><creator>Piersma, Djura</creator><creator>Kapiteijn, Ellen</creator><creator>Labots, Mariette</creator><creator>Boers-Sonderen, Marye J.</creator><creator>van der Veldt, Astrid A.M.</creator><creator>Haanen, John B.A.G.</creator><creator>May, Anne M.</creator><creator>Suijkerbuijk, Karijn P.M.</creator><general>Elsevier Ltd</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>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20240801</creationdate><title>Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma</title><author>Verheijden, Rik J. ; Burgers, Femke H. ; Janssen, Josephine C. ; Putker, Anouk E. ; Veenstra, Sophie P.G.R. ; Hospers, Geke A.P. ; Aarts, Maureen J.B. ; Hehenkamp, Karel W. ; Doornebosch, Veerle L.E. ; Verhaert, Marthe ; van den Berkmortel, Franchette W.P.J. ; Chatzidionysiou, Katerina ; Llobell, Arturo ; Barros, Milton ; Maria, Alexandre T.J. ; Takeji, Akari ; García Morillo, José-Salvador ; Lidar, Merav ; van Eijs, Mick J.M. ; Blank, Christian U. ; Aspeslagh, Sandrine ; Piersma, Djura ; Kapiteijn, Ellen ; Labots, Mariette ; Boers-Sonderen, Marye J. ; van der Veldt, Astrid A.M. ; Haanen, John B.A.G. ; May, Anne M. ; Suijkerbuijk, Karijn P.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c319t-9b7ca5c649c8297980e9542c7c444836c0c6fc7612d1ebef6576ef912d3fcf663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adrenal Cortex Hormones - adverse effects</topic><topic>Adrenal Cortex Hormones - therapeutic use</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Checkpoint inhibitor</topic><topic>Corticosteroids</topic><topic>Female</topic><topic>Humans</topic><topic>Immune Checkpoint Inhibitors - adverse effects</topic><topic>Immune-related adverse events</topic><topic>Immunosuppression</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Male</topic><topic>Melanoma</topic><topic>Melanoma - drug therapy</topic><topic>Melanoma - immunology</topic><topic>Melanoma - mortality</topic><topic>Middle Aged</topic><topic>Retrospective Studies</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Skin Neoplasms - immunology</topic><topic>Skin Neoplasms - mortality</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Verheijden, Rik J.</creatorcontrib><creatorcontrib>Burgers, Femke H.</creatorcontrib><creatorcontrib>Janssen, Josephine C.</creatorcontrib><creatorcontrib>Putker, Anouk E.</creatorcontrib><creatorcontrib>Veenstra, Sophie P.G.R.</creatorcontrib><creatorcontrib>Hospers, Geke A.P.</creatorcontrib><creatorcontrib>Aarts, Maureen J.B.</creatorcontrib><creatorcontrib>Hehenkamp, Karel W.</creatorcontrib><creatorcontrib>Doornebosch, Veerle L.E.</creatorcontrib><creatorcontrib>Verhaert, Marthe</creatorcontrib><creatorcontrib>van den Berkmortel, Franchette W.P.J.</creatorcontrib><creatorcontrib>Chatzidionysiou, Katerina</creatorcontrib><creatorcontrib>Llobell, Arturo</creatorcontrib><creatorcontrib>Barros, Milton</creatorcontrib><creatorcontrib>Maria, Alexandre T.J.</creatorcontrib><creatorcontrib>Takeji, Akari</creatorcontrib><creatorcontrib>García Morillo, José-Salvador</creatorcontrib><creatorcontrib>Lidar, Merav</creatorcontrib><creatorcontrib>van Eijs, Mick J.M.</creatorcontrib><creatorcontrib>Blank, Christian U.</creatorcontrib><creatorcontrib>Aspeslagh, Sandrine</creatorcontrib><creatorcontrib>Piersma, Djura</creatorcontrib><creatorcontrib>Kapiteijn, Ellen</creatorcontrib><creatorcontrib>Labots, Mariette</creatorcontrib><creatorcontrib>Boers-Sonderen, Marye J.</creatorcontrib><creatorcontrib>van der Veldt, Astrid A.M.</creatorcontrib><creatorcontrib>Haanen, John B.A.G.</creatorcontrib><creatorcontrib>May, Anne M.</creatorcontrib><creatorcontrib>Suijkerbuijk, Karijn P.M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>SwePub</collection><collection>SwePub Articles</collection><jtitle>EUROPEAN JOURNAL OF CANCER</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Verheijden, Rik J.</au><au>Burgers, Femke H.</au><au>Janssen, Josephine C.</au><au>Putker, Anouk E.</au><au>Veenstra, Sophie P.G.R.</au><au>Hospers, Geke A.P.</au><au>Aarts, Maureen J.B.</au><au>Hehenkamp, Karel W.</au><au>Doornebosch, Veerle L.E.</au><au>Verhaert, Marthe</au><au>van den Berkmortel, Franchette W.P.J.</au><au>Chatzidionysiou, Katerina</au><au>Llobell, Arturo</au><au>Barros, Milton</au><au>Maria, Alexandre T.J.</au><au>Takeji, Akari</au><au>García Morillo, José-Salvador</au><au>Lidar, Merav</au><au>van Eijs, Mick J.M.</au><au>Blank, Christian U.</au><au>Aspeslagh, Sandrine</au><au>Piersma, Djura</au><au>Kapiteijn, Ellen</au><au>Labots, Mariette</au><au>Boers-Sonderen, Marye J.</au><au>van der Veldt, Astrid A.M.</au><au>Haanen, John B.A.G.</au><au>May, Anne M.</au><au>Suijkerbuijk, Karijn P.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma</atitle><jtitle>EUROPEAN JOURNAL OF CANCER</jtitle><addtitle>Eur J Cancer</addtitle><date>2024-08-01</date><risdate>2024</risdate><volume>207</volume><spage>114172</spage><pages>114172-</pages><artnum>114172</artnum><issn>0959-8049</issn><issn>1879-0852</issn><eissn>1879-0852</eissn><abstract>Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs.
Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression.
Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4–8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4–14) and 55 (95 %CI 41–not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HRadj 1.14; 95 %CI 1.01–1.29; HRadj 1.29; 95 %CI 1.12–1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02–1.72) and OS (HRadj 1.34; 95 %CI 0.99–1.82) compared with corticosteroids alone.
High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.
irAE guidelines advise starting with 1-2 mg/kg prednisone for most ≥grade 3 irAEs.Previous papers suggest that immunosuppression for irAEs impairs survival.Whether this is due to steroid dose or second-line immunosuppression is unknown.We show that both steroid peak dose and second-line immunosuppression are associated with survival.This suggest that it may be better to start with lower steroid doses whenever possible.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>38905818</pmid><doi>10.1016/j.ejca.2024.114172</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0959-8049 |
| ispartof | EUROPEAN JOURNAL OF CANCER, 2024-08, Vol.207, p.114172, Article 114172 |
| issn | 0959-8049 1879-0852 1879-0852 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3071085978 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Adrenal Cortex Hormones - adverse effects Adrenal Cortex Hormones - therapeutic use Adult Aged Aged, 80 and over Checkpoint inhibitor Corticosteroids Female Humans Immune Checkpoint Inhibitors - adverse effects Immune-related adverse events Immunosuppression Immunosuppressive Agents - adverse effects Immunosuppressive Agents - therapeutic use Male Melanoma Melanoma - drug therapy Melanoma - immunology Melanoma - mortality Middle Aged Retrospective Studies Skin Neoplasms - drug therapy Skin Neoplasms - immunology Skin Neoplasms - mortality Toxicity |
| title | Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T23%3A54%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Corticosteroids%20and%20other%20immunosuppressants%20for%20immune-related%20adverse%20events%20and%20checkpoint%20inhibitor%20effectiveness%20in%20melanoma&rft.jtitle=EUROPEAN%20JOURNAL%20OF%20CANCER&rft.au=Verheijden,%20Rik%20J.&rft.date=2024-08-01&rft.volume=207&rft.spage=114172&rft.pages=114172-&rft.artnum=114172&rft.issn=0959-8049&rft.eissn=1879-0852&rft_id=info:doi/10.1016/j.ejca.2024.114172&rft_dat=%3Cproquest_swepu%3E3071085978%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3071085978&rft_id=info:pmid/38905818&rft_els_id=S0959804924008281&rfr_iscdi=true |