The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma

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dc.contributor.authorDaly, Louise E.
dc.contributor.authorPower, Derek G.
dc.contributor.authorO'Reilly, Aine
dc.contributor.authorDonnellan, Paul
dc.contributor.authorCushen, Samantha J.
dc.contributor.authorO'Sullivan, Kathleen
dc.contributor.authorTwomey, Maria
dc.contributor.authorWoodlock, David P.
dc.contributor.authorRedmond, H. Paul
dc.contributor.authorRyan, Aoife M.
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderHealth Research Board
dc.date.accessioned2018-07-30T10:30:31Z
dc.date.available2018-07-30T10:30:31Z
dc.date.issued2017
dc.description.abstractBackground: 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.en
dc.description.sponsorshipHealth Research Board (Clinical Research Facility, Cork (CRF-C)
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDaly, L. E., Power, D. G., O'Reilly, Á., Donnellan, P., Cushen, S. J., O'Sullivan, K., Twomey, M., Woodlock, D. P., Redmond, H. P. and Ryan, A. M. (2017) 'The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma', British Journal of Cancer, 116, pp. 310- 317. doi: 10.1038/bjc.2016.431en
dc.identifier.doi10.1038/bjc.2016.431
dc.identifier.endpage317
dc.identifier.issn0007-0920
dc.identifier.issued3
dc.identifier.journaltitleBritish Journal of Canceren
dc.identifier.startpage310
dc.identifier.urihttps://hdl.handle.net/10468/6520
dc.identifier.volume116
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/
dc.relation.urihttps://www.nature.com/articles/bjc2016431
dc.rights© 2017, Cancer Research UK. All rights reserved. This article is made available under a Creative Commons Attribution-NonCommercial-ShareAlike license.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subjectMetastatic melanomaen
dc.subjectBody compositionen
dc.subjectSarcopeniaen
dc.subjectMuscle attenuationen
dc.subjectToxicityen
dc.subjectNutritional statusen
dc.subjectIpilimumaben
dc.titleThe impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanomaen
dc.typeArticle (peer-reviewed)en
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