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LGG-62. Weight change in pediatric patients treated with MEK inhibitors: a retrospective cohort study
BACKGROUND: MEK inhibition is an emerging treatment strategy in pediatric tumors characterized by activation of the Ras-Raf-MEK-ERK pathway, including low-grade glioma (LGG) and neurofibromatosis 1 (NF1)-associated tumors. Preliminary clinical experience suggests that MEK inhibitors (MEKi) may be as...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165191/ http://dx.doi.org/10.1093/neuonc/noac079.373 |
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author | Hyun Bahng, Hye Malvar, Jemily Chi, Yueh-Yun Framson, Celia Robison, Nathan |
author_facet | Hyun Bahng, Hye Malvar, Jemily Chi, Yueh-Yun Framson, Celia Robison, Nathan |
author_sort | Hyun Bahng, Hye |
collection | PubMed |
description | BACKGROUND: MEK inhibition is an emerging treatment strategy in pediatric tumors characterized by activation of the Ras-Raf-MEK-ERK pathway, including low-grade glioma (LGG) and neurofibromatosis 1 (NF1)-associated tumors. Preliminary clinical experience suggests that MEK inhibitors (MEKi) may be associated with weight gain in children, which has not been a reported toxicity in adults. METHODS: 35 patients > 1 and < 21 years old treated at CHLA with MEKi between October 2013 and May 2019 were identified. Data was collected at t = 0 (baseline), t = 3 months, t = 6 months, t = 12 months, and t = 24 months, as well as pre- and post-treatment time points. Weight change was categorized as no change (change in Z-score [-0.25, +0.25]), weight gain (change in Z-score > 0.25), and weight loss (change in Z-score > -0.25). RESULTS: Weight gain and weight loss were seen in 11 (34.4%) and 8 (25%) patients, respectively, after 6 months on therapy. Weight gain reversed in 4 out of 5 patients with post-treatment data. There was no clear association between weight outcome and hypothesized covariates (including hypothalamic location and NF1 status). Notably, significant weight gain was seen across baseline weight spectrum, including patients who had underweight and severely overweight BMI percentiles at baseline. CONCLUSION: Our findings preliminarily suggest that MEK inhibition may be associated with clinically significant weight change, especially weight gain, in a subset of children and young adults. Reversal upon drug cessation suggests a causal relationship. Further prospective and mechanistic investigation is needed. |
format | Online Article Text |
id | pubmed-9165191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-91651912022-06-05 LGG-62. Weight change in pediatric patients treated with MEK inhibitors: a retrospective cohort study Hyun Bahng, Hye Malvar, Jemily Chi, Yueh-Yun Framson, Celia Robison, Nathan Neuro Oncol Low Grade Glioma BACKGROUND: MEK inhibition is an emerging treatment strategy in pediatric tumors characterized by activation of the Ras-Raf-MEK-ERK pathway, including low-grade glioma (LGG) and neurofibromatosis 1 (NF1)-associated tumors. Preliminary clinical experience suggests that MEK inhibitors (MEKi) may be associated with weight gain in children, which has not been a reported toxicity in adults. METHODS: 35 patients > 1 and < 21 years old treated at CHLA with MEKi between October 2013 and May 2019 were identified. Data was collected at t = 0 (baseline), t = 3 months, t = 6 months, t = 12 months, and t = 24 months, as well as pre- and post-treatment time points. Weight change was categorized as no change (change in Z-score [-0.25, +0.25]), weight gain (change in Z-score > 0.25), and weight loss (change in Z-score > -0.25). RESULTS: Weight gain and weight loss were seen in 11 (34.4%) and 8 (25%) patients, respectively, after 6 months on therapy. Weight gain reversed in 4 out of 5 patients with post-treatment data. There was no clear association between weight outcome and hypothesized covariates (including hypothalamic location and NF1 status). Notably, significant weight gain was seen across baseline weight spectrum, including patients who had underweight and severely overweight BMI percentiles at baseline. CONCLUSION: Our findings preliminarily suggest that MEK inhibition may be associated with clinically significant weight change, especially weight gain, in a subset of children and young adults. Reversal upon drug cessation suggests a causal relationship. Further prospective and mechanistic investigation is needed. Oxford University Press 2022-06-03 /pmc/articles/PMC9165191/ http://dx.doi.org/10.1093/neuonc/noac079.373 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Low Grade Glioma Hyun Bahng, Hye Malvar, Jemily Chi, Yueh-Yun Framson, Celia Robison, Nathan LGG-62. Weight change in pediatric patients treated with MEK inhibitors: a retrospective cohort study |
title | LGG-62. Weight change in pediatric patients treated with MEK inhibitors: a retrospective cohort study |
title_full | LGG-62. Weight change in pediatric patients treated with MEK inhibitors: a retrospective cohort study |
title_fullStr | LGG-62. Weight change in pediatric patients treated with MEK inhibitors: a retrospective cohort study |
title_full_unstemmed | LGG-62. Weight change in pediatric patients treated with MEK inhibitors: a retrospective cohort study |
title_short | LGG-62. Weight change in pediatric patients treated with MEK inhibitors: a retrospective cohort study |
title_sort | lgg-62. weight change in pediatric patients treated with mek inhibitors: a retrospective cohort study |
topic | Low Grade Glioma |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165191/ http://dx.doi.org/10.1093/neuonc/noac079.373 |
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