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The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma
BACKGROUND: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition h...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294486/ https://www.ncbi.nlm.nih.gov/pubmed/28072766 http://dx.doi.org/10.1038/bjc.2016.431 |
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author | Daly, Louise E Power, Derek G O'Reilly, Áine Donnellan, Paul Cushen, Samantha J O'Sullivan, Kathleen Twomey, Maria Woodlock, David P Redmond, Henry P Ryan, Aoife M |
author_facet | Daly, Louise E Power, Derek G O'Reilly, Áine Donnellan, Paul Cushen, Samantha J O'Sullivan, Kathleen Twomey, Maria Woodlock, David P Redmond, Henry P Ryan, Aoife M |
author_sort | Daly, Louise E |
collection | PubMed |
description | BACKGROUND: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established. METHODS: Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Event V.4.0). RESULTS: Eighty-four patients were included in this study (62% male, median age 54 years). At baseline, 24% were sarcopenic and 33% had low MA. On multivariate analysis, sarcopenia and low MA were significantly associated with high-grade AEs (OR=5.34, 95% CI: 1.15–24.88, P=0.033; OR=5.23, 95% CI: 1.41–19.30, P=0.013, respectively), and low MA was associated with high-grade irAEs (OR=3.57, 95% CI: 1.09–11.77, P=0.036). Longitudinal analysis (n=59) revealed significant reductions in skeletal muscle area (SMA), total body fat-free mass, fat mass (all P<0.001) and MA (P=0.030). Mean reduction in SMA was 3.3%/100 days (95% CI: −4.48 to −1.79%, P<0.001). A loss of SMA ⩾7.5%/100 days (highest quartile) was a significant predictor of overall survival in multivariable Cox regression analysis (HR: 2.1, 95% CI: 1.02–4.56, P=0.046). CONCLUSIONS: Patients with sarcopenia and low MA are more likely to experience severe treatment-related toxicity to Ipi. Loss of muscle during treatment was predictive of worse survival. Treatments to increase muscle mass and influence outcome warrant further investigation. |
format | Online Article Text |
id | pubmed-5294486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52944862018-01-31 The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma Daly, Louise E Power, Derek G O'Reilly, Áine Donnellan, Paul Cushen, Samantha J O'Sullivan, Kathleen Twomey, Maria Woodlock, David P Redmond, Henry P Ryan, Aoife M Br J Cancer Clinical Study BACKGROUND: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established. METHODS: Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Event V.4.0). RESULTS: Eighty-four patients were included in this study (62% male, median age 54 years). At baseline, 24% were sarcopenic and 33% had low MA. On multivariate analysis, sarcopenia and low MA were significantly associated with high-grade AEs (OR=5.34, 95% CI: 1.15–24.88, P=0.033; OR=5.23, 95% CI: 1.41–19.30, P=0.013, respectively), and low MA was associated with high-grade irAEs (OR=3.57, 95% CI: 1.09–11.77, P=0.036). Longitudinal analysis (n=59) revealed significant reductions in skeletal muscle area (SMA), total body fat-free mass, fat mass (all P<0.001) and MA (P=0.030). Mean reduction in SMA was 3.3%/100 days (95% CI: −4.48 to −1.79%, P<0.001). A loss of SMA ⩾7.5%/100 days (highest quartile) was a significant predictor of overall survival in multivariable Cox regression analysis (HR: 2.1, 95% CI: 1.02–4.56, P=0.046). CONCLUSIONS: Patients with sarcopenia and low MA are more likely to experience severe treatment-related toxicity to Ipi. Loss of muscle during treatment was predictive of worse survival. Treatments to increase muscle mass and influence outcome warrant further investigation. Nature Publishing Group 2017-01-31 2017-01-10 /pmc/articles/PMC5294486/ /pubmed/28072766 http://dx.doi.org/10.1038/bjc.2016.431 Text en Copyright © 2017 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Clinical Study Daly, Louise E Power, Derek G O'Reilly, Áine Donnellan, Paul Cushen, Samantha J O'Sullivan, Kathleen Twomey, Maria Woodlock, David P Redmond, Henry P Ryan, Aoife M The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma |
title | The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma |
title_full | The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma |
title_fullStr | The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma |
title_full_unstemmed | The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma |
title_short | The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma |
title_sort | impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294486/ https://www.ncbi.nlm.nih.gov/pubmed/28072766 http://dx.doi.org/10.1038/bjc.2016.431 |
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