Symptomatic methemoglobinemia in a patient with metastatic clear cell renal cell carcinoma treated with pembrolizumab and axitinib combination therapy: a case report

• Type of Material: Article
• Authors: T. Anders Olsen, Emory University; Dylan J. Martini, Emory University; Sean T. Evans, Emory University; Jamie Goldman, Emory University; Mehmet Bilen, Emory University
• Language: English
• Date: 2021-12-01
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13256-020-02637-w
• Title of Journal or Parent Work: Journal of Medical Case Reports
• Volume: 15
• Issue: 1
• Start Page: 72
• End Page: 72
• Grant/Funding Information: This work was supported by the Breen Foundation and National Institutes of Health/ National Cancer Institute and the Biostatistics and Bioinformatics Shared Resource of the Winship Cancer Institute of Emory University under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: Humans; Case report; Immunotherapy; Methemoglobinemia; Adverse events and renal cell carcinoma; Axitinib; Kidney Neoplasms; Aged; Carcinoma, Renal Cell; Antibodies, Monoclonal, Humanized; Vascular Endothelial Growth Factor A; Male
• Research Categories: Health Sciences, Immunology; Biology, Cell

Abstract

Background: Combination regimens that include immune checkpoint (ICI) and vascular endothelial growth factor (VEGF) inhibition have opened the door to new treatment opportunities for patients with metastatic renal cell carcinoma (mRCC). While these treatment options have provided improved tolerability and better outcomes compared to older regimens, many patients still experience a myriad of treatment-related adverse events. Given that these regimens were recently approved for mRCC, the complete side effect profile may not be fully elucidated yet. Case presentation: We report a case of a 73-year old White male with mRCC who was managed with an ICI-VEGF inhibitor combination regimen. He experienced a partial response (Fig. 1) but had side effects including symptomatic cyanosis diagnosed as methemoglobinemia which led to treatment discontinuation. Upon holding his therapy, his methemoglobinemia and cyanosis resolved. Conclusions: Combination VEGF-ICI therapy provide novel regimens for advanced solid tumor malignancies including mRCC. While shown to have improved efficacy in clinical trials, it is crucial that oncologists uncover the full side effect profile of these novel agents especially as their use becomes more standard in the management of advanced malignancies. To our knowledge, this is the first reported case of a patient experiencing symptomatic methemoglobinemia as an adverse event associated with a VEGF-ICI combination regimen. While the cause of this side effect is unclear, in this paper we attempt to elucidate a process that is in line with the mechanism of action of these therapies to explain how these agents, specifically the axitinib, could have caused the methemoglobin to rise to a symptomatic level.