Melanoma Metastases to the Adrenal Gland Are Highly Resistant to Immune Checkpoint Inhibitors

Authors:
Jessica S.W. Borgers Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
The Netherlands Cancer Institute, Amsterdam, the Netherlands; and

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 MD
,
Richard P. Tobin Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
Center for Rare Melanomas,
International Melanoma Biorepository, Center for Rare Melanomas,

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 PhD
,
Robert J. Torphy Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado;

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Victoria M. Vorwald Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
Center for Rare Melanomas,
International Melanoma Biorepository, Center for Rare Melanomas,

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Robert J. Van Gulick Center for Rare Melanomas,
International Melanoma Biorepository, Center for Rare Melanomas,
Division of Medical Oncology, Department of Medicine,

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Carol M. Amato Center for Rare Melanomas,
International Melanoma Biorepository, Center for Rare Melanomas,
Division of Medical Oncology, Department of Medicine,

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Dasha T. Cogswell Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
Center for Rare Melanomas,
International Melanoma Biorepository, Center for Rare Melanomas,

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Tugs-Saikhan Chimed Division of Medical Oncology, Department of Medicine,

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Kasey L. Couts International Melanoma Biorepository, Center for Rare Melanomas,
Division of Medical Oncology, Department of Medicine,

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Adrie Van Bokhoven Department of Pathology, and

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Christopher D. Raeburn Division of GI, Trauma, and Endocrine Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

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Karl D. Lewis International Melanoma Biorepository, Center for Rare Melanomas,
Division of Medical Oncology, Department of Medicine,

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Joshua Wisell International Melanoma Biorepository, Center for Rare Melanomas,
Department of Pathology, and

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Martin D. McCarter Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
Center for Rare Melanomas,
International Melanoma Biorepository, Center for Rare Melanomas,

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Rao R. Mushtaq Division of Medical Oncology, Department of Medicine,

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William A. Robinson Center for Rare Melanomas,
International Melanoma Biorepository, Center for Rare Melanomas,
Division of Medical Oncology, Department of Medicine,

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 MD, PhD
Volume/Issue:
Volume 19: Issue 13
Online Publication Date:
31 Dec 2021
DOI:
https://doi.org/10.6004/jnccn.2020.7800
Restricted access

Background: Adrenal gland metastases (AGMs) are common in advanced-stage melanoma, occurring in up to 50% of patients. The introduction of immune checkpoint inhibitors (ICIs) has markedly altered the outcome of patients with melanoma. However, despite significant successes, anecdotal evidence has suggested that treatment responses in AGMs are significantly lower than in other metastatic sites. We sought to investigate whether having an AGM is associated with altered outcomes and whether ICI responses are dampened in the adrenal glands. Patients and Methods: We retrospectively compared ICI responses and overall survival (OS) in 68 patients with melanoma who were diagnosed with an AGM and a control group of 100 patients without AGMs at a single institution. Response was determined using RECIST 1.1. OS was calculated from time of ICI initiation, anti–PD-1 initiation, initial melanoma diagnosis, and stage IV disease diagnosis. Tumor-infiltrating immune cells were characterized in 9 resected AGMs using immunohistochemical analysis. Results: Response rates of AGMs were significantly lower compared with other metastatic sites in patients with AGMs (16% vs 22%) and compared with those without AGMs (55%). Patients with AGMs also had significantly lower median OS compared with those without AGMs (3.1 years vs not reached, respectively). We further observed that despite this, AGMs exhibited high levels of tumor-infiltrating immune cells. Conclusions: In this cohort of patients with melanoma, those diagnosed with an AGM had lower ICI response rates and OS. These results suggest that tissue-specific microenvironments of AGMs present unique challenges that may require novel, adrenal gland–directed therapies or surgical resection.

Submitted June 1, 2020; final revision received December 15, 2020; accepted for publication December 16, 2020.

Published online August 4, 2021.

Author contributions: Study concept and design: All authors. Data acquisition: All authors. Data analysis and interpretation: All authors. Manuscript preparation: All authors. Final approval: All authors.

Disclosures: Dr. Lewis has disclosed receiving grant/research support and personal fees from Roche/Genentech. Dr. McCarter has disclosed receiving grant/research support from Merck & Co., Inc. Dr. Mushtaq has disclosed owning stock and having other ownership interests in Abbott Laboratories, Amgen, Boston Scientific, Bristol Myers Squibb, Celgene Corp Company, Edwards Lifesciences, Gilead Sciences, Johnson & Johnson, and Medtronic. The remaining authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported in part by funding from the Patten-Davis Foundation, the Moore Family Foundation, the University of Colorado Department of Surgery Academic Enrichment Fund, University of Colorado Cancer Center Support Grant (P30CA046934), and the Cancer League of Colorado.

Correspondence: William A. Robinson, MD, PhD, Center for Rare Melanomas, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue, MS8117, Aurora, CO 80045. Email: william.robinson@cuanschutz.edu

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Print ISSN:
1540-1405
Online ISSN:
1540-1413
Publisher:
National Comprehensive Cancer Network
Cover Journal of the National Comprehensive Cancer Network
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Copyright:
Copyright © 2021 by the National Comprehensive Cancer Network 2021
Page Numbers:
11
Article Category:
Research Article
Received:
01 Jun 2020
Accepted:
16 Dec 2020
Print Publication Date:
31 Dec 2021
Online Publication Date:
31 Dec 2021

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