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Cutaneous toxicities of mitogen-activated protein kinase inhibitors in children and young adults with neurofibromatosis-1

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Abstract

Purpose

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder which commonly causes neoplasms leading to disfigurement or dysfunction. Mitogen-activated protein kinase inhibitors (MEKi) are generally well-tolerated treatments which target neural tumor progression in patients with NF1. However, cutaneous adverse events (CAEs) are common and may hinder patients’ abilities to remain on treatment, particularly in children. We aim to characterize CAEs secondary to MEKi treatment in pediatric and young adult patients with NF1.

Methods

We reviewed institutional medical records of patients under 30 years with a diagnosis of “NF1,” “NF2,” or “other neurofibromatoses” on MEKi therapy between January 1, 2019 and June 1, 2022. We recorded the time-to-onset, type, and distribution of CAEs, non-cutaneous adverse events (AEs), AE management, and tumor response.

Results

Our cohort consisted of 40 patients with NF1 (median age, 14 years). Tumor types included low-grade gliomas (51%) and plexiform neurofibromas (38%). MEKi used included selumetinib (69%), trametinib (25%), and mirdametinib (6%). A total of 74 CAEs occurred, with 28 cases of acneiform rash (38%). Other common CAEs were paronychia, seborrheic dermatitis, eczema, xerosis, and oral mucositis. The most common treatments included oral antibiotics and topical corticosteroids. Most patients had clinical (stable or improved) tumor response (71%) while 29% had tumor progression while on a MEKi. There was no significant association between CAE presence and tumor response (p = 0.39).

Conclusions

Improvement in characterization of MEKi toxicities and their management is important to develop treatment guidelines for pediatric and young adult patients with NF1 on MEKi therapy.

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Data availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in a controlled database at MD Anderson Cancer Center.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Author notes

  1. Brianna C. Peacock and Sanjna Tripathy contributed equally to the manuscript.

Authors and Affiliations

  1. Texas A&M University School of Engineering Medicine, Houston, TX, USA

    Brianna C. Peacock

  2. McGovern Medical School, The University of Texas Health Sciences Center, Houston, TX, USA

    Sanjna Tripathy

  3. Baylor College of Medicine, Houston, TX, USA

    Hannah L. Hanania & Hannah Y. Wang

  4. Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Zsila Sadighi

  5. Department of Dermatology, Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 1452, Houston, TX, 77030, USA

    Anisha B. Patel

Authors
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Contributions

A.B.P. conceived of the project. A.B.P. and Z.S. created a framework for data collection carried out by B.C.P. and S.T. Analysis and interpretation of results were performed by H.L.H., B.C.P., and S.T. B.C.P., S.T., and H.Y.W. drafted the manuscript under the supervision of A.B.P. and Z.S. A.B.P. provided critical feedback on the manuscript and all authors reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Anisha B. Patel.

Ethics declarations

Ethical approval

Approval was granted by the Institutional Review Board (IRB) of MD Anderson Cancer Center (Dec 2015, PA15-0959).

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The authors have no relevant financial or non-financial interests to disclose.

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Peacock, B.C., Tripathy, S., Hanania, H.L. et al. Cutaneous toxicities of mitogen-activated protein kinase inhibitors in children and young adults with neurofibromatosis-1. J Neurooncol (2024). https://doi.org/10.1007/s11060-024-04617-2

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