Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study

Abstract Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased eff...
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Autor*in:	Beckmann, Malte [verfasserIn] Schlüter, Julian [verfasserIn] Erdmann, Michael [verfasserIn] Kramer, Rafaela [verfasserIn] Cunningham, Sarah [verfasserIn] Hackstein, Holger [verfasserIn] Zimmermann, Robert [verfasserIn] Heinzerling, Lucie [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Immune checkpoint inhibitors BRAF/MEK inhibitors Melanoma Coagulation–fibrinolysis disorders ICI-associated thrombosis Predictive marker

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: Cancer immunology immunotherapy - Springer Berlin Heidelberg, 1976, 74(2024), 1 vom: 02. Nov.
Übergeordnetes Werk:	volume:74 ; year:2024 ; number:1 ; day:02 ; month:11

Links:	Volltext

DOI / URN:	10.1007/s00262-024-03850-y

Katalog-ID:	SPR058247181

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spelling	10.1007/s00262-024-03850-y doi (DE-627)SPR058247181 (SPR)s00262-024-03850-y-e DE-627 ger DE-627 rakwb eng 610 VZ 610 VZ 44.81 bkl 44.45 bkl Beckmann, Malte verfasserin aut Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies. Immune checkpoint inhibitors (dpeaa)DE-He213 BRAF/MEK inhibitors (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Coagulation–fibrinolysis disorders (dpeaa)DE-He213 ICI-associated thrombosis (dpeaa)DE-He213 Predictive marker (dpeaa)DE-He213 Schlüter, Julian verfasserin aut Erdmann, Michael verfasserin aut Kramer, Rafaela verfasserin aut Cunningham, Sarah verfasserin aut Hackstein, Holger verfasserin aut Zimmermann, Robert verfasserin aut Heinzerling, Lucie verfasserin aut Enthalten in Cancer immunology immunotherapy Springer Berlin Heidelberg, 1976 74(2024), 1 vom: 02. Nov. (DE-627)253390443 (DE-600)1458489-X 1432-0851 nnns volume:74 year:2024 number:1 day:02 month:11 https://dx.doi.org/10.1007/s00262-024-03850-y X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4277 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.81 VZ 44.45 VZ AR 74 2024 1 02 11
allfields_unstemmed	10.1007/s00262-024-03850-y doi (DE-627)SPR058247181 (SPR)s00262-024-03850-y-e DE-627 ger DE-627 rakwb eng 610 VZ 610 VZ 44.81 bkl 44.45 bkl Beckmann, Malte verfasserin aut Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies. Immune checkpoint inhibitors (dpeaa)DE-He213 BRAF/MEK inhibitors (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Coagulation–fibrinolysis disorders (dpeaa)DE-He213 ICI-associated thrombosis (dpeaa)DE-He213 Predictive marker (dpeaa)DE-He213 Schlüter, Julian verfasserin aut Erdmann, Michael verfasserin aut Kramer, Rafaela verfasserin aut Cunningham, Sarah verfasserin aut Hackstein, Holger verfasserin aut Zimmermann, Robert verfasserin aut Heinzerling, Lucie verfasserin aut Enthalten in Cancer immunology immunotherapy Springer Berlin Heidelberg, 1976 74(2024), 1 vom: 02. Nov. (DE-627)253390443 (DE-600)1458489-X 1432-0851 nnns volume:74 year:2024 number:1 day:02 month:11 https://dx.doi.org/10.1007/s00262-024-03850-y X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4277 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.81 VZ 44.45 VZ AR 74 2024 1 02 11
allfieldsGer	10.1007/s00262-024-03850-y doi (DE-627)SPR058247181 (SPR)s00262-024-03850-y-e DE-627 ger DE-627 rakwb eng 610 VZ 610 VZ 44.81 bkl 44.45 bkl Beckmann, Malte verfasserin aut Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies. Immune checkpoint inhibitors (dpeaa)DE-He213 BRAF/MEK inhibitors (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Coagulation–fibrinolysis disorders (dpeaa)DE-He213 ICI-associated thrombosis (dpeaa)DE-He213 Predictive marker (dpeaa)DE-He213 Schlüter, Julian verfasserin aut Erdmann, Michael verfasserin aut Kramer, Rafaela verfasserin aut Cunningham, Sarah verfasserin aut Hackstein, Holger verfasserin aut Zimmermann, Robert verfasserin aut Heinzerling, Lucie verfasserin aut Enthalten in Cancer immunology immunotherapy Springer Berlin Heidelberg, 1976 74(2024), 1 vom: 02. Nov. (DE-627)253390443 (DE-600)1458489-X 1432-0851 nnns volume:74 year:2024 number:1 day:02 month:11 https://dx.doi.org/10.1007/s00262-024-03850-y X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4277 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.81 VZ 44.45 VZ AR 74 2024 1 02 11
allfieldsSound	10.1007/s00262-024-03850-y doi (DE-627)SPR058247181 (SPR)s00262-024-03850-y-e DE-627 ger DE-627 rakwb eng 610 VZ 610 VZ 44.81 bkl 44.45 bkl Beckmann, Malte verfasserin aut Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies. Immune checkpoint inhibitors (dpeaa)DE-He213 BRAF/MEK inhibitors (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Coagulation–fibrinolysis disorders (dpeaa)DE-He213 ICI-associated thrombosis (dpeaa)DE-He213 Predictive marker (dpeaa)DE-He213 Schlüter, Julian verfasserin aut Erdmann, Michael verfasserin aut Kramer, Rafaela verfasserin aut Cunningham, Sarah verfasserin aut Hackstein, Holger verfasserin aut Zimmermann, Robert verfasserin aut Heinzerling, Lucie verfasserin aut Enthalten in Cancer immunology immunotherapy Springer Berlin Heidelberg, 1976 74(2024), 1 vom: 02. Nov. (DE-627)253390443 (DE-600)1458489-X 1432-0851 nnns volume:74 year:2024 number:1 day:02 month:11 https://dx.doi.org/10.1007/s00262-024-03850-y X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4277 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.81 VZ 44.45 VZ AR 74 2024 1 02 11
language	English
source	Enthalten in Cancer immunology immunotherapy 74(2024), 1 vom: 02. Nov. volume:74 year:2024 number:1 day:02 month:11
sourceStr	Enthalten in Cancer immunology immunotherapy 74(2024), 1 vom: 02. Nov. volume:74 year:2024 number:1 day:02 month:11
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Immune checkpoint inhibitors BRAF/MEK inhibitors Melanoma Coagulation–fibrinolysis disorders ICI-associated thrombosis Predictive marker
dewey-raw	610
isfreeaccess_bool	true
container_title	Cancer immunology immunotherapy
authorswithroles_txt_mv	Beckmann, Malte @@aut@@ Schlüter, Julian @@aut@@ Erdmann, Michael @@aut@@ Kramer, Rafaela @@aut@@ Cunningham, Sarah @@aut@@ Hackstein, Holger @@aut@@ Zimmermann, Robert @@aut@@ Heinzerling, Lucie @@aut@@
publishDateDaySort_date	2024-11-02T00:00:00Z
hierarchy_top_id	253390443
dewey-sort	3610
id	SPR058247181
language_de	englisch
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author	Beckmann, Malte
spellingShingle	Beckmann, Malte ddc 610 bkl 44.81 bkl 44.45 misc Immune checkpoint inhibitors misc BRAF/MEK inhibitors misc Melanoma misc Coagulation–fibrinolysis disorders misc ICI-associated thrombosis misc Predictive marker Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study
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topic_title	610 VZ 44.81 bkl 44.45 bkl Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study Immune checkpoint inhibitors (dpeaa)DE-He213 BRAF/MEK inhibitors (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Coagulation–fibrinolysis disorders (dpeaa)DE-He213 ICI-associated thrombosis (dpeaa)DE-He213 Predictive marker (dpeaa)DE-He213
topic	ddc 610 bkl 44.81 bkl 44.45 misc Immune checkpoint inhibitors misc BRAF/MEK inhibitors misc Melanoma misc Coagulation–fibrinolysis disorders misc ICI-associated thrombosis misc Predictive marker
topic_unstemmed	ddc 610 bkl 44.81 bkl 44.45 misc Immune checkpoint inhibitors misc BRAF/MEK inhibitors misc Melanoma misc Coagulation–fibrinolysis disorders misc ICI-associated thrombosis misc Predictive marker
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title	Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study
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title_full	Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study
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author_browse	Beckmann, Malte Schlüter, Julian Erdmann, Michael Kramer, Rafaela Cunningham, Sarah Hackstein, Holger Zimmermann, Robert Heinzerling, Lucie
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title_sort	interdependence of coagulation with immunotherapy and braf/mek inhibitor therapy: results from a prospective study
title_auth	Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study
abstract	Abstract Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies. © The Author(s) 2024
abstractGer	Abstract Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies. © The Author(s) 2024
abstract_unstemmed	Abstract Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies. © The Author(s) 2024
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title_short	Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study
url	https://dx.doi.org/10.1007/s00262-024-03850-y
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author2	Schlüter, Julian Erdmann, Michael Kramer, Rafaela Cunningham, Sarah Hackstein, Holger Zimmermann, Robert Heinzerling, Lucie
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