title: The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma.
abstract: 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.
  
  
  
  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).
  
  
  
  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).
  
  
  
  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.
authors.affiliation: School of Food and Nutritional Sciences/APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: Louise E
authors.initials: LE
authors.lastname: Daly
authors.affiliation: Department of Medical Oncology, Cork University Hospital, Cork, Ireland.
authors.forename: Derek G
authors.initials: DG
authors.lastname: Power
authors.affiliation: Department of Medical Oncology, University Hospital Galway, Galway, Ireland.
authors.forename: Áine
authors.initials: Á
authors.lastname: O'Reilly
authors.affiliation: Department of Medical Oncology, University Hospital Galway, Galway, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Donnellan
authors.affiliation: School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Cushen
authors.affiliation: School of Mathematical Science, University College Cork, Cork, Ireland.
authors.forename: Kathleen
authors.initials: K
authors.lastname: O'Sullivan
authors.affiliation: Department of Radiology, Cork University Hospital, Cork, Ireland.
authors.forename: Maria
authors.initials: M
authors.lastname: Twomey
authors.affiliation: Department of Radiology, University Hospital Galway, Galway, Ireland.
authors.forename: David P
authors.initials: DP
authors.lastname: Woodlock
authors.affiliation: Department of Surgery, Cork University Hospital and University College Cork, Cork, Ireland.
authors.forename: Henry P
authors.initials: HP
authors.lastname: Redmond
authors.affiliation: School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Ryan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D001823:Body Composition / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D055948:Sarcopenia / Q000401:mortality; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab