Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition

Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Naik, Girish S. [verfasserIn] Waikar, Sushrut S. Johnson, Alistair E. W. Buchbinder, Elizabeth I. Haq, Rizwan Hodi, F. Stephen Schoenfeld, Jonathan D. Ott, Patrick A.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Anti-PD-1 Melanoma Body mass index Creatinine Obesity paradox

Anmerkung:	© The Author(s). 2019

Übergeordnetes Werk:	Enthalten in: Journal for ImmunoTherapy of Cancer - London : BioMed Central, 2013, 7(2019), 1 vom: 29. März
Übergeordnetes Werk:	volume:7 ; year:2019 ; number:1 ; day:29 ; month:03

Links:	Volltext

DOI / URN:	10.1186/s40425-019-0512-5

Katalog-ID:	SPR036438596

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520			\|a Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination).
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allfields	10.1186/s40425-019-0512-5 doi (DE-627)SPR036438596 (SPR)s40425-019-0512-5-e DE-627 ger DE-627 rakwb eng Naik, Girish S. verfasserin aut Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). Anti-PD-1 (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Body mass index (dpeaa)DE-He213 Creatinine (dpeaa)DE-He213 Obesity paradox (dpeaa)DE-He213 Waikar, Sushrut S. aut Johnson, Alistair E. W. aut Buchbinder, Elizabeth I. aut Haq, Rizwan aut Hodi, F. Stephen aut Schoenfeld, Jonathan D. aut Ott, Patrick A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 29. März (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:29 month:03 https://dx.doi.org/10.1186/s40425-019-0512-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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 AR 7 2019 1 29 03
spelling	10.1186/s40425-019-0512-5 doi (DE-627)SPR036438596 (SPR)s40425-019-0512-5-e DE-627 ger DE-627 rakwb eng Naik, Girish S. verfasserin aut Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). Anti-PD-1 (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Body mass index (dpeaa)DE-He213 Creatinine (dpeaa)DE-He213 Obesity paradox (dpeaa)DE-He213 Waikar, Sushrut S. aut Johnson, Alistair E. W. aut Buchbinder, Elizabeth I. aut Haq, Rizwan aut Hodi, F. Stephen aut Schoenfeld, Jonathan D. aut Ott, Patrick A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 29. März (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:29 month:03 https://dx.doi.org/10.1186/s40425-019-0512-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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 AR 7 2019 1 29 03
allfields_unstemmed	10.1186/s40425-019-0512-5 doi (DE-627)SPR036438596 (SPR)s40425-019-0512-5-e DE-627 ger DE-627 rakwb eng Naik, Girish S. verfasserin aut Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). Anti-PD-1 (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Body mass index (dpeaa)DE-He213 Creatinine (dpeaa)DE-He213 Obesity paradox (dpeaa)DE-He213 Waikar, Sushrut S. aut Johnson, Alistair E. W. aut Buchbinder, Elizabeth I. aut Haq, Rizwan aut Hodi, F. Stephen aut Schoenfeld, Jonathan D. aut Ott, Patrick A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 29. März (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:29 month:03 https://dx.doi.org/10.1186/s40425-019-0512-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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 AR 7 2019 1 29 03
allfieldsGer	10.1186/s40425-019-0512-5 doi (DE-627)SPR036438596 (SPR)s40425-019-0512-5-e DE-627 ger DE-627 rakwb eng Naik, Girish S. verfasserin aut Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). Anti-PD-1 (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Body mass index (dpeaa)DE-He213 Creatinine (dpeaa)DE-He213 Obesity paradox (dpeaa)DE-He213 Waikar, Sushrut S. aut Johnson, Alistair E. W. aut Buchbinder, Elizabeth I. aut Haq, Rizwan aut Hodi, F. Stephen aut Schoenfeld, Jonathan D. aut Ott, Patrick A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 29. März (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:29 month:03 https://dx.doi.org/10.1186/s40425-019-0512-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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 AR 7 2019 1 29 03
allfieldsSound	10.1186/s40425-019-0512-5 doi (DE-627)SPR036438596 (SPR)s40425-019-0512-5-e DE-627 ger DE-627 rakwb eng Naik, Girish S. verfasserin aut Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). Anti-PD-1 (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Body mass index (dpeaa)DE-He213 Creatinine (dpeaa)DE-He213 Obesity paradox (dpeaa)DE-He213 Waikar, Sushrut S. aut Johnson, Alistair E. W. aut Buchbinder, Elizabeth I. aut Haq, Rizwan aut Hodi, F. Stephen aut Schoenfeld, Jonathan D. aut Ott, Patrick A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 29. März (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:29 month:03 https://dx.doi.org/10.1186/s40425-019-0512-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 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_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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 AR 7 2019 1 29 03
language	English
source	Enthalten in Journal for ImmunoTherapy of Cancer 7(2019), 1 vom: 29. März volume:7 year:2019 number:1 day:29 month:03
sourceStr	Enthalten in Journal for ImmunoTherapy of Cancer 7(2019), 1 vom: 29. März volume:7 year:2019 number:1 day:29 month:03
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Anti-PD-1 Melanoma Body mass index Creatinine Obesity paradox
isfreeaccess_bool	true
container_title	Journal for ImmunoTherapy of Cancer
authorswithroles_txt_mv	Naik, Girish S. @@aut@@ Waikar, Sushrut S. @@aut@@ Johnson, Alistair E. W. @@aut@@ Buchbinder, Elizabeth I. @@aut@@ Haq, Rizwan @@aut@@ Hodi, F. Stephen @@aut@@ Schoenfeld, Jonathan D. @@aut@@ Ott, Patrick A. @@aut@@
publishDateDaySort_date	2019-03-29T00:00:00Z
hierarchy_top_id	750086335
id	SPR036438596
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR036438596</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519225917.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2019 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s40425-019-0512-5</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR036438596</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s40425-019-0512-5-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Naik, Girish S.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s). 2019</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. 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author	Naik, Girish S.
spellingShingle	Naik, Girish S. misc Anti-PD-1 misc Melanoma misc Body mass index misc Creatinine misc Obesity paradox Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition
authorStr	Naik, Girish S.
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topic_title	Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition Anti-PD-1 (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Body mass index (dpeaa)DE-He213 Creatinine (dpeaa)DE-He213 Obesity paradox (dpeaa)DE-He213
topic	misc Anti-PD-1 misc Melanoma misc Body mass index misc Creatinine misc Obesity paradox
topic_unstemmed	misc Anti-PD-1 misc Melanoma misc Body mass index misc Creatinine misc Obesity paradox
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title	Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition
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title_full	Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition
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author_browse	Naik, Girish S. Waikar, Sushrut S. Johnson, Alistair E. W. Buchbinder, Elizabeth I. Haq, Rizwan Hodi, F. Stephen Schoenfeld, Jonathan D. Ott, Patrick A.
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title_sort	complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition
title_auth	Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition
abstract	Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). © The Author(s). 2019
abstractGer	Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). © The Author(s). 2019
abstract_unstemmed	Background A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma in the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) in a pooled meta-analysis. We characterized the relationship of Body Mass Index (BMI) with survival and explored gender-based interactions with surrogates of body composition/malnutrition in the context of PD-1 blockade as monotherapy or in combination with ipilimumab in a real-world setting. Methods Advanced melanoma patients who received at least one dose of pembrolizumab, nivolumab, or nivolumab plus ipilimumab (combination) from June 2014 to September 2016 were included in this retrospective cohort study (N = 139). Overall Survival (OS) and Progression Free Survival (PFS) were the main outcomes. Analysis was performed using Random Survival Forests (RSF)/ multivariable Cox Proportional-Hazards models. Results Overweight/Class-I (25- < 35 kg/$ m^{2} $) obese patients had a significantly lower risk of mortality (adjusted-HR:0.26; 95%CI:0.1–0.71; p-value = 0.008) and progressive disease (adjusted-HR:0.43; 95%CI:0.19–0.95; p-value:0.038) compared to normal-weight (18.5- < 25 kg/$ m^{2} $). Class II/III obesity (compared to normal-weight) had an adjusted HR of 0.42 (95%CI: 0.1–1.77; p-value: 0.238) for OS and 1 (95%CI:0.34–2.94; p-value:0.991) for PFS. Exploration of interactions for OS showed that the association was predominantly driven by males (adjusted-$ HR_{males} $:0.11; 95%CI:0.03–0.4; adjusted-$ HR_{females} $: 0.56; 95%CI:0.16–1.$ 89_{;} $p-$ value_{interaction} $:0.044); the association was not seen in patients with serum creatinine< 0.9 mg/dL (adjusted-HR:0.43; 95%CI:0.15–1.24; p-$ value_{interaction} $:0.020), who were predominantly females. These observations were made in both the anti-PD-1 monotherapy (n = 79) and combination therapy (anti-PD-1/CTLA-4, n = 60) cohorts. Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarcopenia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). © The Author(s). 2019
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title_short	Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition
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Conclusions The findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. 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Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition

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