循環器ジャーナル69巻4号

2021年10月発行

特集 プレシジョン・メディシン時代における腫瘍循環器学の重要性 Ⅱ章　がん医療の進歩と腫瘍循環器学

がん免疫療法による心血管系の免疫関連有害事象（irAE）

著者： 向井幹夫¹ 塩山渉²

所属機関： ¹地方独立行政法人大阪府立病院機構大阪国際がんセンター成人病ドック科 ²滋賀医科大学循環器内科

ページ範囲：P.570 - P.578

Point
・がん免疫療法はがん患者の予後を改善する一方で，免疫関連有害事象が問題となっている．
・がん免疫関連心毒性，特に劇症型心筋炎は予後が不良であり，早期診断・治療が重要である．
・がん免疫関連心毒性の病態・機序には不明な点が多く，実臨床データの蓄積が待たれる．

参考文献

1) 日本臨床腫瘍学会（編）：がん免疫療法ガイドライン第2版，金原出版，2019

2) Schreiber RD, Old JL, Smyth MJ: Cancer immunoediting:integrating immunity's roles in cancer suppression and promotion. Science 331:1565-1570, 2011

3) Chen DS, Mellman I:Oncology meets immunology:the cancer-immunity cycle. Immunity 39:1-10, 2013

4) Chen DS, Mellman I:Elements of cancer immunity and the cancer-immune set point. Nature 541:321-330, 2017

5) Kawakami Y, Yaguchi T, Sumimoto H, et al:Improvement of cancer immunotherapy by combining molecular targeted therapy. Front Oncol 3:136, 2013

6) June CH, Sadelain M:Chimeric Antigen Receptor Therapy. N Engl J Med 379:64-73, 2018

is a novel multiple myeloma-specific target for CAR T cell therapy. Nat Med 23:1436-1443, 2017

8) Brahmer JR: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 36:1714-1768, 2018

9) Champiat S, Lambotte O, Barreau E, et al:Management of immune checkpoint blockade dysimmune toxicities:a collaborative position paper. Ann Oncol 27:559-574, 2016

10) Thompson JA, Schneider BJ, Brahmer J, et al:Management of Immunotherapy-Related Toxicities, Version 1.2019. J Natl Compr Canc Netw 17:255-289, 2019

11) Wang DY, Salem JE, Cohen JV, et al:Fatal toxic Effects associated with immune checkpoint inhibitors:a systematic review and meta-analysis. JAMA Oncol 4:1721-1728, 2018

12) Johnson DB, Balko JM, Compton ML, et al:Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med 375:1749-1755, 2016

13) Mahmood SS, Fradley MG, Cohen JV, et al:Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 71:1755-1764, 2018

14) Sarocchi M, Grossi F, Arboscello E, et al:Serial troponin for early detection of nivolumab cardiotoxicity in advanced nonsmall cell lung cancer patients. Oncologist 23:936-942, 2018

15) Nishimura H, Okazaki T, Tanaka Y, et al:Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291:319-322, 2001

16) Postow MA, Sidlow R, Hellmann MD:Immune related adverse events associated with immune checkpoint blockade. N Engl J Med 378:158-168, 2018

17) Hu W, Wang G, Wang Y, et al:Uncoupling Therapeutic Efficacyfrom Immune-Related Adverse Eventsin Immune Checkpoint Blockade. iScience 23:101580, 2020

18) Glabie N, Lichtman AH, Padera R:T cell checkpoint regulators in the heart. Cardiovasc Res 115:869-877, 2019

19) Bonaca MP, Olenchock BA, Salem JE, et al:Myocarditis in the setting of cancer therapeutics:Proposed case definitions for emerging clinical syndromes in Cardio-Oncology. Circulation 140:80-91, 2019

20) Moslehi JJ, Salem JE, Sosman JA, et al:Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 391:933, 2018

21) Palaskas N, Lopez-Mattei J, Durand JB, et al:Immune checkpoint inhibitor myocarditis:pathophysiological characteristics, diagnosis, and treatment. J Am Heart Assoc 9:e013757, 2020

22) Oren O, Yang EH, Molina JR, et al:Cardiovascular health and outcomes in cancer patients receiving immune checkpoint inhibitors. Am J Cardiol 125:1920-1926, 2020

23) Ganatra S, Carver JR, Hayek SS, et al:Chimeric antigen receptor T-cell therapy for cancer and heart:JACC Council perspectives. J Am Coll Cardiol 74:3153-3163, 2019

24) Alvi RM, Frigault MJ, Fradley MG, et al:Cardiovascular events among adults treated with chimeric antigen receptor T-cells（CAR-T）. J Am Coll Cardiol 74:3099-3108, 2019

25) Neelapu SS, Locke FL, Bartlett NL, et al:Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 377:2531-2544, 2017

26) Zhang L, Reynolds KL, Lyon AR, et al:The evolving immunotherapy landscape and the epidemiology, diagnosis, and management of cardiotoxicity:JACC:CardioOncology Primer. JACC Cardio Oncol 3:35-47, 2021