Clinical characteristics of 26 cases with endocrine gland diseases related to programmed death receptor-1 (PD1) inhibitors in cancer patients
WANG Qun1, JIANG Jinjin2, LU Zhiqiang2, ZHAO Lin2
(1. Department of Endocrinology, the Fourth Affiliated Hospital of Nanjing Medical University, Nanjing Jiangsu 210000; 2. Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai 200032, China)
Abstract:Objective: To explore the clinical characteristics of endocrine gland diseases related to programmed death receptor1 (PD1) inhibitors in cancer patients. Methods: From January 2020 to December 2020, 26 patients admitted by the Department of Endocrinology, Zhongshan Hospital affiliated to Fudan University were retrospected. All patients showed immune-related adverse events (irAEs) in endocrine system after the administration of PD-1 inhibitors due to cancers. The relationship and clinical features of PD-1 inhibitor induced endocrine gland damages were analyzed. Results: Of 26 patients, 19 were male (73.08%) and 7 were female (26.92%). The average age was (61.62±9.77) years. PD-1 inhibitorassociated hypophysitis was found in 18 cases (69.23%), among whom, the pituitary adrenal axis involvement was found in all cases, adrenal axis and thyroid axis involvement was found in 4 cases, and posterior pituitary lobe involvement was not found. PD-1 inhibitors associated primary thyroid dysfunction was found in 9 patients (34.62%). Related type 1 diabetes was found in 5 cases (19.23%). Autoimmune polyendocrine syndrome (APS) was found in 7 cases (26.92%), including 6 cases involving pituitary and thyroid gland, and 1 case involving pituitary and pancreas. PD-1-related primary adrenal hypofunction was not observed. Conclusion: The endocrine gland related indicators should be evaluated before and during the administration of immune checkpoint inhibitors (ICPis) in cancer patients to reduce misdiagnosis and missed diagnosis, improve safety during the immunotherapy, and enhance the patients′ quality of life.
王群, 蒋晶晶, 陆志强, 赵琳. 程序性死亡受体-1抑制剂相关内分泌腺体疾患26例临床特征分析[J]. 江苏大学学报:医学版, 2023, 33(02): 156-161.
WANG Qun1, JIANG Jinjin2, LU Zhiqiang2, ZHAO Lin2. Clinical characteristics of 26 cases with endocrine gland diseases related to programmed death receptor-1 (PD1) inhibitors in cancer patients. Journal of Jiangsu University(Medicine Edition), 2023, 33(02): 156-161.
[1]Dougan M, Pietropaolo M. Time to dissect the autoimmune etiology of cancer antibody immunotherapy[J]. J Clin Invest, 2020, 130(1): 51-61.
[2]Chang LS, BarrosoSousa R, Tolaney SM, et al. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints[J]. Endocr Rev, 2019, 40(1): 17-65.
[3]Ntali G, Kassi E, Alevizaki M. Endocrine sequelae of immune checkpoint inhibitors[J]. Hormones (Athens), 2017, 16(4): 341-350.
[4]Byun DJ, Wolchok JD, Rosenberg LM, et al. Cancer immunotherapy—immune checkpoint blockade and associated endocrinopathies[J]. Nat Rev Endocrinol, 2017, 13(4): 195-207.
[5]中华医学会内分泌学分会免疫内分泌学组. 免疫检查点抑制剂引起的内分泌系统免疫相关不良反应专家共识(2020)[J], 中华内分泌代谢杂志, 2021, 37(1): 1-16.
[6]Castinetti F, Albarel F, Archambeaud F, et al. French Endocrine Society Guidance on endocrine side effects of immunotherapy[J]. Endocr Relat Cancer, 2019, 26(2): G1-G18.
[7]Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and followup[J]. Ann Oncol, 2017, 28 (suppl 4): iv119-iv142.
[8]Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group[J]. J Immunother Cancer, 2017, 5(1): 95.
[9]Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immunerelated adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline[J]. J Clin Oncol, 2018, 36(17): 1714-1768.
[10]Cancer Care Ontario. Clinical practice guideline: immune checkpoint inhibitor toxicity management[EB/OL]. (2018-03-01)[2020-10-10]. http://guide.medlive.cn/guideline/16186.
[11]Thompson JA. New NCCN Guidelines: Recognition and management of immunotherapyrelated toxicity[J]. J Natl Compr Canc Netw, 2018, 16(5S): 594-596.
[12]Thompson JA, Schneider BJ, Brahmer J, et al. Management of immunotherapyrelated toxicities, version 1. 2019[J]. J Natl Compr Canc Netw, 2019, 17(3): 255-289.
[13]Thompson JA, Schneider BJ, Brahmer J, et al. NCCN Guidelines Insights: Management of immunotherapyrelated toxicities, version 1. 2020[J]. J Natl Compr Canc Netw, 2020, 18(3): 230-241.
[14]中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)免疫检查点抑制剂相关的毒性管理指南(2019 年版)[M]. 北京: 人民卫生出版社, 2019.
[15]曹灵, 李晓牧. 免疫检查抑制剂相关内分泌不良事件[J]. 中国临床医学, 2020, 27(6): 931-937.
[16]Lu J, Li L, Lan Y, et al. Immune checkpoint inhibitorassociated pituitaryadrenal dysfunction: A systematic review and metaanalysis[J]. Cancer Med, 2019, 8(18): 7503-7515.
[17]Wang Y, Zhou S, Yang F, et al. Treatmentrelated adverse events of PD1 and PDL1 inhibitors in clinical trials: A systematic review and metaanalysis[J]. JAMA Oncol, 2019, 5(7): 1008-1019.
[18]Faje A, Reynolds K, Zubiri L, et al. Hypophysitis secondary to nivolumab and pembrolizumab is a clinical entity distinct from ipilimumabassociated hypophysitis[J]. Eur J Endocrinol, 2019, 181(3): 211-219.
[19]BarrosoSousa R, Barry WT, GarridoCastro AC, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: A systematic review and metaanalysis[J]. JAMA Oncol, 2018, 4(2): 173-182.
[20]GaronCzmil J, Petitpain N, Rouby F, et al. Immune check point inhibitorsinduced hypophysitis: a retrospective analysis of the French Pharmacovigilance database[J]. Sci Rep, 2019, 9(1): 19419.
[21]Faje A. Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insights[J]. Pituitary, 2016, 19(1): 82-92.
[22]Bellastella G, Maiorino MI, Bizzarro A, et al. Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects[J]. Pituitary, 2016, 19(6): 625-642.
[23]Mei Y, Bi WL, Greenwald NF, et al. Increased expression of programmed death ligand 1 (PDL1) in human pituitary tumors[J]. Oncotarget, 2016, 7(47): 76565-76576.
[24]de Filette JMK, Pen JJ, Decoster L, et al. Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review[J]. Eur J Endocrinol, 2019, 181(3): 363-374.
[25]Postow MA, Sidlow R, Hellmann MD. Immunerelated adverse events associated with immune checkpoint blockade[J]. N Engl J Med, 2018, 378(2): 158-168.
[26]Orlov S, Salari F, Kashat L, et al. Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies[J]. J Clin Endocrinol Metab, 2015, 100(5): 1738-1741.
[27]Cambridge L, Rizvi H, Wolchok JD, et al. Antibodymediated thyroid dysfunction during Tcell checkpoint blockade in patients with nonsmallcell lung cancer[J]. Ann Oncol, 2017, 28(3): 583-589.
[28]Maekura T, Naito M, Tahara M, et al. Predictive factors of nivolumabinduced hypothyroidism in patients with nonsmall cell lung cancer[J]. In Vivo, 2017, 31(5): 1035-1039.
[29]Gauci ML, Laly P, VidalTrecan T, et al. Autoimmune diabetes induced by PD1 inhibitorretrospective analysis and pathogenesis: a case report and literature review[J]. Cancer Immunol Immunother, 2017, 66(11): 1399-1410.
[30]Stamatouli AM, Quandt Z, Perdigoto AL, et al. Collateral damage: insulindependent diabetes induced with checkpoint inhibitors[J]. Diabetes, 2018, 67(8): 1471-1480.
[31]Imagawa A, Hanafusa T, Awata T, et al. Report of the Committee of the Japan Diabetes Society on the research of fulminant and acuteonset type 1 diabetes mellitus: New diagnostic criteria of fulminant type 1 diabetes mellitus(2012)[J]. J Diabetes Investig, 2012, 3(6): 536-539.