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Клинический случай осложнения иммунотерапии – энцефалит
© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.
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Lyadova MA, Kuchevskaya OA, Kulikova EA. Clinical case of complications of immunotherapy – encephalitis. Journal of Modern Oncology. 2023;25(1):140–144. DOI: 10.26442/18151434.2023.1.202168
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Ключевые слова: ингибиторы контрольных точек иммунитета, иммунотерапия, атезолизумаб, мелкоклеточный рак легкого, иммуноопосредованные нежелательные явления, энцефалит
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Nowadays, checkpoint inhibitors are widely used in the treatment of various types of cancer. However, its’ use is often accompanied by the development of immune-mediated adverse events (IAEs) of various systems and organs. Aim – description of the features of the development of encephalitis during the treatment of small cell lung cancer (SCLC) using checkpoint inhibitors. There is a clinical case of a patient, who is receiving immunotherapy, with small cell carcinoma of the upper lobe of the left lung, stage IVA, cT2bN2M1a. The patient sought medical help in connection with complaints of an episode of memory loss, difficulty in remembering new information. Based on the clinical picture and examination data, a limbic encephalitis was diagnosed. Immune-related adverse events might affect any organ during all the period of therapy with checkpoint inhibitors. Physicians shall be aware of the risk of encephalitis development related to this type of anti-cancer therapy.
Keywords: immune checkpoint inhibitors, immunotherapy, atezolizumab, small cell lung cancer, immune-mediated adverse events, encephalitis
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31. Leitinger M, Varosanec MV, Pikija S, et al. Fatal necrotizing encephalopathy after treatment with nivolumab for squamous non-small cell lung cancer: case report and review of the literature. Front Immunol. 2018;9:108. DOI:10.3389/fimmu.2018.00108
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1. Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020;17(8):807-21. DOI:10.1038/s41423-020-0488-6
2. Bagchi S, Yuan R, Engleman EG. Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance. Annu Rev Pathol. 2021;16:223-49. DOI:10.1146/annurev-pathol-042020-042741
3. Chhabra N, Kennedy J. A Review of Cancer Immunotherapy Toxicity: Immune Checkpoint Inhibitors. J Med Toxicol. 2021;17(4):411-24. DOI:10.1007/s13181-021-00833-8
4. Topalian SL, Taube JM, Pardoll DM. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science. 2020;367(6477):eaax0182. DOI:10.1126/science.aax0182
5. Corrales L, Gajewski TF. Endogenous and pharmacologic targeting of the STING pathway in cancer immunotherapy. Cytokine. 2016;77:245-7. DOI:10.1016/j.cyto.2015.08.258
6. Jenkins MK. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med. 1987;165(2):302-19. DOI:10.1084/jem.165.2.302
7. Yshii LM, Hohlfeld R, Liblau RS. Inflammatory CNS disease caused by immune checkpoint inhibitors: status and perspectives. Nat Rev Neurol. 2017;13(12):755-63. DOI:10.1038/nrneurol.2017.144
8. Gibson HM, Hedgcock CJ, Aufiero BM, et al. Induction of the CTLA-4 gene in human lymphocytes is dependent on NFAT binding the proximal promoter. J Immunol. 2007;179(6):3831-40. DOI:10.4049/jimmunol.179.6.3831
9. Zheng Y, Josefowicz SZ, Kas A, et al. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature. 2007;445(7130):936-40. DOI:10.1038/nature05563
10. Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, et al. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 2012;209(6):1201-17. DOI:10.1084/jem.20112741
11. Granier C, De Guillebon E, Blanc C, et al. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open. 2017;2(2):e000213.
DOI:10.1136/esmoopen-2017-000213
12. Dalakas MC. Neurological complications of immune checkpoint inhibitors: what happens when you ‘take the brakes off’ the immune system. Ther Adv Neurol Disord. 2018;11:1756286418799864. DOI:10.1177/1756286418799864
13. Kyi C, Carvajal RD, Wolchok JD, Postow MA. Ipilimumab in patients with melanoma and autoimmune disease. J Immunother Cancer. 2014;2(1):35. DOI:10.1186/s40425-014-0035-z
14. Sato K, Akamatsu H, Murakami E, et al. Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab. Lung Cancer. 2018;115:71-4. DOI:10.1016/j.lungcan.2017.11.019
15. Bomze D, Hasan Ali O, Bate A, Flatz L. Association between immune-related adverse events during anti-PD-1 therapy and tumor mutational burden. JAMA Oncol. 2019; 5(11):1633-5. DOI:10.1001/jamaoncol.2019.3221
16. Balachandran VP, Łuksza M, Zhao JN, et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature. 2017;551(7681):512-6. DOI:10.1038/nature24462
17. Weiss MD, Luciano CA, Semino-Mora C, et al. Molecular mimicry in chronic inflammatory demyelinating polyneuropathy and melanoma. Neurology. 1998;51(6):1738-41. DOI:10.1212/wnl.51.6.1738
18. Gerdes LA, Held K, Beltrán E, et al. CTLA4 as immunological checkpoint in the development of multiple sclerosis: CTLA4 and MS. Ann Neurol. 2016;80(2):294-300. DOI:10.1002/ana.24715
19. Wang DY, Salem JE, Cohen JV, et al. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(12):1721-8. DOI:10.1001/jamaoncol.2018.3923
20. Martins F, Sofiya L, Sykiotis GP, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;16(9):563-80. DOI:10.1038/s41571-019-0218-0
21. Dubey D, David WS, Reynolds KL, et al. Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum. Ann Neurol. 2020;87(5):659-69. DOI:10.1002/ana.25708
22. Johnson DB, McDonnell WJ, Gonzalez-Ericsson PI, et al. A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis. Nat Med. 2019;25(8):1243-50. DOI:10.1038/s41591-019-0523-2
23. Johnson DB, Manouchehri A, Haugh AM, et al. Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study. J Immunother Cancer. 2019;7(1):134. DOI:10.1186/s40425-019-0617-x
24. Fan S, Ren H, Zhao L, et al. Neurological immune-related adverse events associated with immune checkpoint inhibitors: A review of the literature. Asia Pac J Clin Oncol. 2020;16(6):291-8. DOI:10.1111/ajco.13375
25. Schneider S, Potthast S, Komminoth P, et al. PD-1 checkpoint inhibitor associated autoimmune encephalitis. Case Rep Oncol. 2017;10(2):473-8. DOI:10.1159/000477162
26. Richard K, Weslow J, Porcella SL, Nanjappa S. A case report of steroid responsive nivolumab-induced encephalitis. Cancer Control. 2017;24(5):1073274817729069. DOI:10.1177/1073274817729069
27. Procenko SA, Antimonik NJu, Balljuzek MF, et al. Practical Guidelines for the Management of immune-related adverse events. Zlokachestvennie opuholi: Prakticheskie rekomendacii RUSSCO #3s2. 2022;12(3S2-2):203-41 (in Russian). DOI:10.18027/2224-5057-2022-12-3s2-203-241
28. Conry RM, Sullivan JC, Nabors LB. Ipilimumab-induced encephalopathy with a reversible splenial lesion. Cancer Immunol Res. 2015;3(6):598-601. DOI:10.1158/2326-6066.CIR-15-0035
29. Salam S, Lavin T, Turan A. Limbic encephalitis following immunotherapy against metastatic malignant melanoma. BMJ Case Rep. 2016;bcr2016215012. DOI:10.1136/bcr-2016-215012
30. Schmitt SE, Pargeon K, Frechette ES, et al. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology. 2012;79:1094-100. DOI:10.1212/WNL.0b013e3182698cd8
31. Leitinger M, Varosanec MV, Pikija S, et al. Fatal necrotizing encephalopathy after treatment with nivolumab for squamous non-small cell lung cancer: case report and review of the literature. Front Immunol. 2018;9:108. DOI:10.3389/fimmu.2018.00108
32. Vitt JR, Kreple C, Mahmood N, et al. Autoimmune pancerebellitis associated with pembrolizumab therapy. Neurology. 2018;91(2):91-3. DOI:10.1212/WNL.0000000000005781
33. Weil AA, Glaser CA, Amad Z, Forghani B. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis. 2002;34(8):1154-7. DOI:10.1086/339550
ГБУЗ «Городская клиническая онкологическая больница №1» Департамента здравоохранения г. Москвы, Москва, Россия
*dr.lyadova@gmail.com
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Marina A. Lyadova*, Olesya A. Kuchevskaya, Evgeniya A. Kulikova
City Clinical Oncology Hospital №1, Moscow, Russia
*dr.lyadova@gmail.com