Immunotherapy-Induced Acute Hepatitis in the Elderly: The Case of a Patient with Urothelial Carcinoma and a Review of the Literature

[1] Martins F, Sofiya L, Sykiotis GP, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;May 15. doi:10.1038/s41571-019-0218-0. MartinsF SofiyaL SykiotisGP Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance Nat Rev Clin Oncol 2019 May 15 10.1038/s41571-019-0218-0 31092901 Open DOISearch in Google Scholar

[2] Postow M, Wolchok J. Patient selection criteria and toxicities associated with checkpoint inhibitor immunotherapy 2018. Uptodate.com. PostowM WolchokJ Patient selection criteria and toxicities associated with checkpoint inhibitor immunotherapy 2018 Uptodate.com. Search in Google Scholar

[3] Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; Jul 1;28(suppl_4):iv119–iv142. doi:10.1093/annonc/mdx225. HaanenJBAG CarbonnelF RobertC Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up Ann Oncol 2017 Jul 1 28 suppl_4 iv119 iv142 10.1093/annonc/mdx225 28881921 Open DOISearch in Google Scholar

[4] Johncilla M, Misdraji J, Pratt DS, et al. Ipilimumab-associated hepatitis: clinicopathologic characterization in a series of 11 cases. Am J Surg Pathol. 2015;39. JohncillaM MisdrajiJ PrattDS Ipilimumab-associated hepatitis: clinicopathologic characterization in a series of 11 cases Am J Surg Pathol 2015 39 10.1097/PAS.000000000000045326034866 Search in Google Scholar

[5] Kim KW, Ramaiya NH, Krajewski KM, et al. Ipilimumab associated hepatitis: imaging and clinicopathological findings. Invest New Drugs. 2013;31. KimKW RamaiyaNH KrajewskiKM Ipilimumab associated hepatitis: imaging and clinicopathological findings Invest New Drugs 2013 31 10.1007/s10637-013-9939-623408334 Search in Google Scholar

[6] Karamchandani, D. M., Chetty, R. Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective. J Clin Pathol. 2018;71: 665–671. KaramchandaniD. M. ChettyR. Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective J Clin Pathol 2018 71 665 671 10.1136/jclinpath-2018-20514329703758 Search in Google Scholar

[7] Ziemer M, Koukoulioti E, Beyer S, et al. Managing immune checkpoint-inhibitor-induced severe autoimmune-like hepatitis by liver-directed topical steroids. J Hepatology. 2017;66(3):657–659. ZiemerM KoukouliotiE BeyerS Managing immune checkpoint-inhibitor-induced severe autoimmune-like hepatitis by liver-directed topical steroids J Hepatology 2017 66 3 657 659 10.1016/j.jhep.2016.11.01527908801 Search in Google Scholar

[8] Aivazian K., et al. Histopathology of pembrolizumab-induced hepatitis: a case report. Pathology. 2017;49(7):789–792. AivazianK. Histopathology of pembrolizumab-induced hepatitis: a case report Pathology 2017 49 7 789 792 10.1016/j.pathol.2017.07.01029079004 Search in Google Scholar

[9] Friedman CF, Horvat TZ, Minehart J, et al. Efficacy and safety of checkpoint blockade for treatment of advanced melanoma (mel) in patients (pts) age 80 and older (80+). J Clin Oncology. 2016;34(15_Suppl.):10009. FriedmanCF HorvatTZ MinehartJ Efficacy and safety of checkpoint blockade for treatment of advanced melanoma (mel) in patients (pts) age 80 and older (80+) J Clin Oncology 2016 34 15_Suppl. 10009 10.1200/JCO.2016.34.15_suppl.10009 Search in Google Scholar

[10] European Medicine Agency Keytruda (pembrolizumab) authorization. https://www.ema.europa.eu/en/medicines/human/EPAR/keytruda. European Medicine Agency Keytruda (pembrolizumab) authorization https://www.ema.europa.eu/en/medicines/human/EPAR/keytruda. Search in Google Scholar

[11] Wu Z, Lai L, Li M, Zhang L, Zhang W. Acute liver failure caused by pembrolizumab in a patient with pulmonary metastatic liver cancer: A case report. Medicine (Baltimore). 2017;96(51):e9431. doi:10.1097/MD.0000000000009431. WuZ LaiL LiM ZhangL ZhangW Acute liver failure caused by pembrolizumab in a patient with pulmonary metastatic liver cancer: A case report Medicine (Baltimore) 2017 96 51 e9431 10.1097/MD.0000000000009431 575827429390572 Open DOISearch in Google Scholar

[12] Naidoo J, Page DB, Li BT, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26:2375–2591. NaidooJ PageDB LiBT Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies Ann Oncol 2015 26 2375 2591 10.1093/annonc/mdv383626786726371282 Search in Google Scholar

[13] Elias R, Karantanos T, Sira E, et al. Immunotherapy comes of age: immune aging & checkpoint inhibitors. J Geriatr Oncol. 2017;8(3):229–235. EliasR KarantanosT SiraE Immunotherapy comes of age: immune aging & checkpoint inhibitors J Geriatr Oncol 2017 8 3 229 235 10.1016/j.jgo.2017.02.00128223073 Search in Google Scholar

[14] Daste A, Domblides C, Gross-Goupil M, et al. Immune checkpoint inhibitors and elderly people: a review. Eur J Cancer. 2017;82:155–166. DasteA DomblidesC Gross-GoupilM Immune checkpoint inhibitors and elderly people: a review Eur J Cancer 2017 82 155 166 10.1016/j.ejca.2017.05.04428689093 Search in Google Scholar

[15] Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2018;Jun 10;36(17):1714–1768. doi:10.1200/JCO.2017.77.6385. BrahmerJR LacchettiC SchneiderBJ Management of immune related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline J Clin Oncol 2018 Jun 10 36 17 1714 1768 10.1200/JCO.2017.77.6385 648162129442540 Open DOISearch in Google Scholar

[16] Thompson JA, Schneider BJ, Brahmer J et al. Management of immunotherapy related toxicities, Version 2.2019–April 8, 2019. NCCN Clinical Practice Guidelines in Oncology. ThompsonJA SchneiderBJ BrahmerJ Management of immunotherapy related toxicities, Version 2.2019–April 8, 2019 NCCN Clinical Practice Guidelines in Oncology Search in Google Scholar

[17] Suzman DL, Pelosof L, Rosenberg A, et al. Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents. Liver Int, 2018;38:976–987. SuzmanDL PelosofL RosenbergA Hepatotoxicity of immune checkpoint inhibitors: An evolving picture of risk associated with a vital class of immunotherapy agents Liver Int 2018 38 976 987 10.1111/liv.1374629603856 Search in Google Scholar

[18] Kleiner DE, Berman D. Pathologic changes in ipilimumab-related hepatitis in patients with metastatic melanoma. Dig Dis Sci. 2012;57:2233. KleinerDE BermanD Pathologic changes in ipilimumab-related hepatitis in patients with metastatic melanoma Dig Dis Sci 2012 57 2233 10.1007/s10620-012-2140-5379248522434096 Search in Google Scholar

[19] Holstein Y, Kapiteijn E, Bastiaannet E, van den Bos F, Portielje J, de Glas NA. Efficacy and adverse events of immunotherapy with checkpoint inhibitors in older patients with cancer. Drugs Aging. 2019 Oct;36(10):927–938. doi:10.1007/s40266-019-00697-2. PMID: 31317421; PMCID: PMC6764930. HolsteinY KapiteijnE BastiaannetE van den BosF PortieljeJ de GlasNA Efficacy and adverse events of immunotherapy with checkpoint inhibitors in older patients with cancer Drugs Aging 2019 Oct 36 10 927 938 10.1007/s40266-019-00697-2 PMID: 31317421; PMCID: PMC6764930 676493031317421 Open DOISearch in Google Scholar

[20] Singh H, Kim G, Maher VE, et al. FDA subset analysis of the safety of nivolumab in elderly patients with advanced cancers. J Clin Oncology. 2016;34(15_Suppl.):10010. SinghH KimG MaherVE FDA subset analysis of the safety of nivolumab in elderly patients with advanced cancers J Clin Oncology 2016 34 15_Suppl. 10010 10.1200/JCO.2016.34.15_suppl.10010 Search in Google Scholar

[21] Gomes F, Woolley S, Califano R, et al. MA 1007 elderly lung cancer patients on immunotherapy: preliminary results from the ELDERS study. J Thorac Oncol. 2017;12(11):S1841–1842. GomesF WoolleyS CalifanoR MA 1007 elderly lung cancer patients on immunotherapy: preliminary results from the ELDERS study J Thorac Oncol 2017 12 11 S1841 1842 10.1016/j.jtho.2017.09.538 Search in Google Scholar

[22] Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376:1015. BellmuntJ de WitR VaughnDJ Pembrolizumab as second-line therapy for advanced urothelial carcinoma N Engl J Med 2017 376 1015 10.1056/NEJMoa1613683563542428212060 Search in Google Scholar

[23] Balar AV, Castellano D, O’Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol 2017;18:1483. BalarAV CastellanoD O’DonnellPH First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study Lancet Oncol 2017 18 1483 10.1016/S1470-2045(17)30616-228967485 Search in Google Scholar

[24] U.S. Department of Health and Human Services National Institutes of Health National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0. November 27, 2017. U.S. Department of Health and Human Services National Institutes of Health National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0 November 27 2017 Search in Google Scholar

[25] Chmiel KD, Suan D, Liddle C. Resolution of severe ipilimumab-induced hepatitis after antithymocyte globulin therapy. J Clin Oncol. 2011;Mar;29(9):e237–40. ChmielKD SuanD LiddleC Resolution of severe ipilimumab-induced hepatitis after antithymocyte globulin therapy J Clin Oncol 2011 Mar 29 9 e237 40 10.1200/JCO.2010.32.220621220617 Search in Google Scholar