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The impact of body composition parameters on severe toxicity of nivolumab.
Eur J Cancer 2020; 124:170-177EJ

Abstract

BACKGROUND

The occurrence of severe, acute limiting toxicity in patients receiving anti-programmed cell death receptor-1 monoclonal antibodies, such as nivolumab, is largely unpredictable. Sarcopenia was found to be associated with anti-cytotoxic T-lymphocyte-associated protein 4 acute toxicity. We explore the clinical and pharmacological parameters influencing nivolumab toxicity, including body composition.

METHODS

From June 2015 to January 2017, all consecutive patients treated with nivolumab in our institution were prospectively included. We studied the relationship between muscle mass assessed by computed tomography, nivolumab trough level (Cmin) at day 14 assessed using the enzyme-linked immunosorbent assay method, and the occurrence of immune grade III or IV toxicity or any toxicity leading to treatment discontinuation (immune-related acute limiting toxicity [irALT]).

RESULTS

In our population (n = 92) with a majority of lung cancer (72%), forty-five (51.7%) patients were sarcopenic. The median plasma nivolumab Cmin at day 14 was 15.4 μg/mL (interquartile range = 11.8-21.0). In multivariate analysis, hypoalbuminaemia (<35 g/L) was independently associated with low nivolumab Cmin on day 14 (odds ratio [OR] = 0.09; 95% confidence interval [CI] = 0.01-0.59, p = 0.01) and overweight/obesity with high nivolumab Cmin on day 14 (OR = 5.94; 95% CI = 1.25-28.29, p = 0.03). We observed 22 irALTs in 19 patients (21%). The most frequent irALT was respiratory (6.5%) disorders and gastrointestinal (4.3%) disorders. Patients with sarcopenia were at significantly increased risk of experiencing an irALT (OR = 3.84; 95% CI = 1.02-14.46, p = 0.047). No association was found between toxicity and nivolumab plasma Cmin at day 14.

CONCLUSIONS

Our results highlight the importance of assessing body composition and suggest that sarcopenia could predict severe immune-related toxicity of nivolumab in real life.

Authors+Show Affiliations

Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France. Electronic address: laure.hirsch@wanadoo.fr.Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France.Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France.Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France.Department of Clinical Pharmacy, Cochin Hospital, AP-HP 5, CERTIM, Paris, France; UMR8038 CNRS, U1268 INSERM, Faculty of Pharmacy, Université Paris Descartes, PRES Sorbonne Paris Cité, 75006, Paris, France.Department of Gastroenterology, Saint-Antoine Hospital, AP-HP 6, Paris, France; Sorbonne Université, INSERM, Institut Pierre Louis D'Épidémiologie et de Santé Publique, Paris, France.Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France.Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France; Cochin Institute, Inserm U1016, Université Paris Descartes, Paris, France.Department of Pneumology, Cochin Hospital, AP-HP 5, Paris, France.Department of Pneumology, Cochin Hospital, AP-HP 5, Paris, France.Department of Pneumology, Cochin Hospital, AP-HP 5, Paris, France; Cordeliers Research Center, Université Paris Descartes, Université de Paris, UMRS1138 "Inflammation, Complement and Cancer" Team, F-75006, Paris, France.Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France; Cochin Institute, Inserm U1016, Université Paris Descartes, Paris, France.UMR8038 CNRS, U1268 INSERM, Faculty of Pharmacy, Université Paris Descartes, PRES Sorbonne Paris Cité, 75006, Paris, France; Department of Pharmacokinetics and Pharmacochemisty, Cochin Hospital, AP-HP 5, CARPEM, Paris, France.Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France; Laboratory of Biological Nutrition EA, Pharmacy University, Université Paris Descartes, 4466, Paris, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31794927

Citation

Hirsch, Laure, et al. "The Impact of Body Composition Parameters On Severe Toxicity of Nivolumab." European Journal of Cancer (Oxford, England : 1990), vol. 124, 2020, pp. 170-177.
Hirsch L, Bellesoeur A, Boudou-Rouquette P, et al. The impact of body composition parameters on severe toxicity of nivolumab. Eur J Cancer. 2020;124:170-177.
Hirsch, L., Bellesoeur, A., Boudou-Rouquette, P., Arrondeau, J., Thomas-Schoemann, A., Kirchgesner, J., ... Goldwasser, F. (2020). The impact of body composition parameters on severe toxicity of nivolumab. European Journal of Cancer (Oxford, England : 1990), 124, pp. 170-177. doi:10.1016/j.ejca.2019.11.003.
Hirsch L, et al. The Impact of Body Composition Parameters On Severe Toxicity of Nivolumab. Eur J Cancer. 2020;124:170-177. PubMed PMID: 31794927.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The impact of body composition parameters on severe toxicity of nivolumab. AU - Hirsch,Laure, AU - Bellesoeur,Audrey, AU - Boudou-Rouquette,Pascaline, AU - Arrondeau,Jennifer, AU - Thomas-Schoemann,Audrey, AU - Kirchgesner,Julien, AU - Gervais,Claire, AU - Jouinot,Anne, AU - Chapron,Jeanne, AU - Giraud,Frédérique, AU - Wislez,Marie, AU - Alexandre,Jérôme, AU - Blanchet,Benoit, AU - Goldwasser,François, Y1 - 2019/11/30/ PY - 2019/07/10/received PY - 2019/10/25/revised PY - 2019/11/04/accepted PY - 2019/12/4/pubmed PY - 2019/12/4/medline PY - 2019/12/4/entrez KW - Body composition KW - Lung cancer KW - Nivolumab KW - Pharmacology KW - Toxicity SP - 170 EP - 177 JF - European journal of cancer (Oxford, England : 1990) JO - Eur. J. Cancer VL - 124 N2 - BACKGROUND: The occurrence of severe, acute limiting toxicity in patients receiving anti-programmed cell death receptor-1 monoclonal antibodies, such as nivolumab, is largely unpredictable. Sarcopenia was found to be associated with anti-cytotoxic T-lymphocyte-associated protein 4 acute toxicity. We explore the clinical and pharmacological parameters influencing nivolumab toxicity, including body composition. METHODS: From June 2015 to January 2017, all consecutive patients treated with nivolumab in our institution were prospectively included. We studied the relationship between muscle mass assessed by computed tomography, nivolumab trough level (Cmin) at day 14 assessed using the enzyme-linked immunosorbent assay method, and the occurrence of immune grade III or IV toxicity or any toxicity leading to treatment discontinuation (immune-related acute limiting toxicity [irALT]). RESULTS: In our population (n = 92) with a majority of lung cancer (72%), forty-five (51.7%) patients were sarcopenic. The median plasma nivolumab Cmin at day 14 was 15.4 μg/mL (interquartile range = 11.8-21.0). In multivariate analysis, hypoalbuminaemia (<35 g/L) was independently associated with low nivolumab Cmin on day 14 (odds ratio [OR] = 0.09; 95% confidence interval [CI] = 0.01-0.59, p = 0.01) and overweight/obesity with high nivolumab Cmin on day 14 (OR = 5.94; 95% CI = 1.25-28.29, p = 0.03). We observed 22 irALTs in 19 patients (21%). The most frequent irALT was respiratory (6.5%) disorders and gastrointestinal (4.3%) disorders. Patients with sarcopenia were at significantly increased risk of experiencing an irALT (OR = 3.84; 95% CI = 1.02-14.46, p = 0.047). No association was found between toxicity and nivolumab plasma Cmin at day 14. CONCLUSIONS: Our results highlight the importance of assessing body composition and suggest that sarcopenia could predict severe immune-related toxicity of nivolumab in real life. SN - 1879-0852 UR - https://www.unboundmedicine.com/medline/citation/31794927/The_impact_of_body_composition_parameters_on_severe_toxicity_of_nivolumab L2 - https://linkinghub.elsevier.com/retrieve/pii/S0959-8049(19)30810-X DB - PRIME DP - Unbound Medicine ER -