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. 2024 Sep 11;28(5):423.
doi: 10.3892/etm.2024.12712. eCollection 2024 Nov.

Cytokine release syndrome and immune effector cell‑associated neurotoxicity syndrome in a melanoma patient treated with adjuvant pembrolizumab

Sebastian Ochenduszko  1 , Lamberto Landete  2 , David Collado Martinez  3 , Ana García Feria  4 , Carla Francés  5 , María Dolores Torregrosa  1 , Inmaculada Maestu Maiques  1
Affiliations

Cytokine release syndrome and immune effector cell‑associated neurotoxicity syndrome in a melanoma patient treated with adjuvant pembrolizumab

Sebastian Ochenduszko et al. Exp Ther Med. .

Abstract

The emergence of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with solid tumors. However, along with their efficacy, new toxicities related to immune system activation have surfaced, some of which pose life-threatening risks. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are among the serious, albeit rare, immune-related adverse effects (irAEs) observed. Although commonly associated with hematologic malignancies and chimeric antigen receptor T cell therapies, CRS has been reported in patients treated with ICIs, with ICANS being a less documented complication. The present study presents a case report of a 76-year-old patient with resected melanoma who developed clinical symptoms of CRS and ICANS following adjuvant pembrolizumab therapy. The patient presented with neurological symptoms of weakness and encephalopathy with confusion, bradypsychia, dysarthria, tremors and visual hallucinations. Laboratory tests revealed elevated serum levels of tumor necrosis factor-alpha and interleukin-6 along with inflammatory markers, hepatic and renal dysfunction, as well as rapidly progressive normochromic-normocytic anemia. Treatment with corticosteroids led to rapid symptom resolution, albeit with subsequent symptom recurrence after tapering its dose. This case underscores the importance of recognizing and managing irAEs associated with ICIs and highlights the need for vigilant monitoring and individualized therapeutic approaches.

Keywords: ICANS; cytokine release syndrome; immune checkpoint inhibitors.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
TNF-alpha level changes according to prednisone daily dose and the moment of symptoms recurrence. Dashed line indicates the upper limit of normal. TNF-alpha, tumor necrosis factor alpha.
Figure 2
Figure 2
IL-6 level changes according to prednisone daily dose and the moment of symptoms recurrence. Dashed line indicates the upper limit of normal.
See this image and copyright information in PMC

References

    1. Wesley SF, Haggiagi A, Thakur KT, De Jager PL. Neurological immunotoxicity from cancer treatment. Int J Mol Sci. 2021;22(6716) doi: 10.3390/ijms22136716. - DOI - PMC - PubMed
    1. Ceschi A, Noseda R, Palin K, Verhamme K. Immune checkpoint inhibitor-related cytokine release Syndrome: Analysis of WHO global pharmacovigilance database. Front Pharmacol. 2020;11(557) doi: 10.3389/fphar.2020.00557. - DOI - PMC - PubMed
    1. Liu LL, Skribek M, Harmenberg U, Gerling M. Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: Case report and systematic review of the literature. J Immunother Cancer. 2023;11(e005841) doi: 10.1136/jitc-2022-005841. - DOI - PMC - PubMed
    1. Hamida O, Karlsson F, Lundqvist A, Gerling M, Liu LL. Cytokine release syndrome after treatment with immune checkpoint inhibitors: An observational cohort study of 2672 patients from Karolinska University Hospital in Sweden. Oncoimmunology. 2024;13(2372875) doi: 10.1080/2162402X.2024.2372875. - DOI - PMC - PubMed
    1. Tay SH, Toh MMX, Thian YL, Vellayappan BA, Fairhurst AM, Chan YH, Aminkeng F, Bharwani LD, Huang Y, Mak A, Wong ASC. Cytokine release syndrome in cancer patients receiving immune checkpoint inhibitors: A case series of 25 patients and review of the literature. Front Immunol. 2022;13(807050) doi: 10.3389/fimmu.2022.807050. - DOI - PMC - PubMed

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