Fatální myokarditida po první dávce nivolumabu

Stiahnuť PDF English version

Autori: E. Zomborska ¹; S. Kasperova ²; J. Slopovsky ¹; N. Pazderová ¹; B. Kasperova ³; P. Penz ⁴; O. Nyitrayová ⁵; T. Salek ¹; S. Porsok ¹; B. Mladosievicova ⁶; M. Mego ¹
Pôsobisko autorov: National Cancer Institute, Bratislava, Slovak Republic ; 2nd Department of Oncology, Comenius University, Faculty of Medicine and National Cancer Institute, Bratislava, Slovak Republic ¹; 1st Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic ²; Department of Oncohematology, Faculty of Medicine, Comenius University, Slovakia ³; Department of Dia gnostic and Interventional Radiology, National Heart Institute, Bratislava, Slovak Republic ⁴; Biopsy centrum Cytophatos, Bratislava, Slovak Republic ⁵; Institute of Pathological Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic ⁶
Vyšlo v časopise: Klin Onkol 2022; 35(6): 486-492
Kategória: Case Reports
doi: https://doi.org/10.48095/ccko2022486

Súhrn

Východiska: Karcinom thymu (thymic carcinoma – TC) je vzácným podtypem malignity thymu epiteliálního původu. Stěžejní součástí léčby TC je chirurgická resekce, zatímco radioterapie a chemoterapie jsou modality, které se používají v adjuvantním nebo paliativním režimu. Checkpoint inhibitory, kam patří protilátky proti receptoru programované buněčné smrti 1 (programmed cell death 1 – PD-1), představují nově vznikající modalitu léčby TC, nicméně jejich podávání může být spojeno s život ohrožující toxicitou. Případ: Prezentujeme případ 59leté ženy s grade III TC, které byla podána neoadjuvantní chemoterapie, po které následoval chirurgický zákrok a následně byla podána adjuvantní radioimunoterapie s checkpoint inhibitorem, nivolumabem. V článku sdělujeme naše zkušenosti s toxicitou podávaného přípravku. Výsledky: Čtrnáct dní po první dávce nivolumabu a 21. den po zahájení radioterapie (v celkové dávce 40 Gy) se u pacientky rozvinula fulminantní myokarditida s následným srdečním selháním. I přes imunosupresivní terapii vysokodávkovými glukokortikoidy a mykofenolát mofetilem a přes intenzivní podpůrnou terapii pacientka během 6 dní od nástupu prvních symptomů zemřela. Závěr: Lékaři by měli mít na paměti tyto extrémně vzácné, avšak potenciálně fatální komplikace imunoterapie.

Klíčová slova:

nivolumab – imunoterapie – checkpoint inhibitory – kardiotoxicita – karcinom thymu

Zdroje

1. Agrawal B. New therapeutic targets for cancer: the interplay between immune and metabolic checkpoints and gut microbiota. Clin Transl Med 2019; 8 (1): 23. doi: 10.1186/s40169-019-0241-x.

2. Bayat Mokhtari R, Homayouni TS, Baluch N et al. Combination therapy in combating cancer. Oncotarget 2017; 8 (23): 38022–38043. doi: 10.18632/oncotarget.16723.

3. Yeung SJ, Qdaisat A, Chaftari P et al. Diagnosis and management of immune-related adverse effects of immune checkpoint therapy in the emergency department. J Am Coll Emerg Physicians Open 2020; 1 (6): 1637–1659. doi: 10.1002/emp2.12209.

4. Hsu HC, Huang EY, Wang CJ et al. Postoperative radiotherapy in thymic carcinoma: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys 2002; 52 (3): 801–805. doi: 10.1002/emp2.12209.

5. Berghmans T, Durieux V, Holbrechts S et al. Systemic treatments for thymoma and thymic carcinoma: a systematic review. Lung Cancer 2018; 126: 25–31. doi: 10.1016/j.lungcan.2018.10.018.

6. Luo Y, Li JL, Yang L et al. Chemotherapy with gemcitabine plus cisplatin in patients with advanced thymic squamous cell carcinoma: evaluation of efficacy and toxicity. Thorac Cancer 2016; 7 (2): 167–172. doi: 10.1111/1759-7714.12300.

7. Zander T, Aebi S, Rast AC et al. Response to pembrolizumab in a patient with relapsing thymoma. J Thorac Oncol 2016; 11 (12): e147–e149. doi: 10.1016/j.jtho.2016.07.018.

8. Yang PC, Guo JC, Hsieh MS et al. Response to nivolumab as salvage therapy in a patient with thymic carcinoma. J Thorac Oncol 2018; 13 (3): e36–e39. doi: 10.1016/j.jtho.2017.10.022.

9. Katsuya Y, Horinouchi H, Seto T et al. Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study. Eur J Cancer 2019; 113: 78–86. doi: 10.1016/j.ejca.2019.03.012.

10. Giaccone G, Kim C, Thompson J et al. Pembrolizumab in patients with thymic carcinoma: a single-arm, single--centre, phase 2 study. Lancet Oncol 2018; 19 (3): 347–355. doi: 10.1016/S1470-2045 (18) 30062-7.

11. Cho J, Kim HS, Mi Ku B et al. Pembrolizumab for patients with refractory or relapsed thymic epithelial tumor: an open-label phase II trial. J Clin Oncol 2019; 37 (24): 2162–2170. doi: 10.1200/JCO.2017.77.3184.

12. Zhao C, Rajan A. Immune checkpoint inhibitors for treatment of thymic epithelial tumors: how to maximize benefit and optimize risk? Mediastinum 2019; 3: 35. doi: 10.21037/med.2019.08.02.

13. Rajan A, Heery CR, Thomas A et al. Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma. J Immunother Cancer 2019; 7 (1): 269. doi: 10.1186/s40425-019-0723-9.

14. Choi J, Lee SY. Clinical characteristics and treatment of immune-related adverse events of immune checkpoint inhibitors. Immune Netw 2020; 20 (1): e9. doi: 10.4110/in.2020.20.e9.

15. Matsuo K, Ishiguro T, Najama T et al. Nivolumab-induced myocarditis successfully treated with corticosteroid therapy: a case report and review of the literature. Intern Med 2019; 58 (16): 2367–2372. doi: 10.2169/internalmedicine.2596-18.

16. Moslehi JJ, Salem JE, Sosman JA et al. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 2018; 391 (10124): 933. doi: 10.1016/S0140-6736 (18) 30533-6.

17. Chen Q, Huang DS, Zhang LW et al. Fatal myocarditis and rhabdomyolysis induced by nivolumab during the treatment of type B3 thymoma. Clin Toxicol (Phila) 2018; 56 (7): 667–671. doi: 10.1080/15563650.2017.1401079.

18. Wang DY, Okoye GD, Neilan TG et al. Cardiovascular toxicities associated with cancer immunotherapies. Curr Cardiol Rep 2017; 19 (3): 21. doi: 10.1007/s11886-017-0835-0.

19. Frigeri M, Meyer P, Banfi C et al. Immune checkpoint inhibitor-associated myocarditis: a new challenge for cardiologists. Can J Cardiol 2018; 34 (1): 92e1–92e3. doi: 10.1016/j.cjca.2017.09.025.

20. Agostinetto E, Eiger D, Lambertini M et al. Cardiotoxicity of immune checkpoint inhibitors: a systematic review and meta-analysis of randomised clinical trials. Eur J Cancer 2021; 148: 76–91. doi: 10.1016/j.ejca.2021.01.043.

21. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018; 378 (2): 158–168. doi: 10.1056/NEJMra1703481.

22. Muller OJ, Spehlmann ME, Frey N. Cardio-toxicity of checkpoint inhibitors. J Thorac Dis 2018; 10 (Suppl 35): S4400–S4404. doi: 10.21037/jtd.2018.12.78.

23. Ball S, Ghosh RK, Wongsaengsak S et al. Cardiovascular toxicities of immune checkpoint inhibitors: JACC review topic of the week. J Am Coll Cardiol 2019; 74 (13): 1714–1727. doi: 10.1016/j.jacc.2019.07.079.

24. Anscher MS, Arora S, Weinstock C et al. Impact of radiotherapy on risk of adverse events in patients receiving immunotherapy: a U.S. food and drug administration pooled analysis. J Clin Oncol 2020; 38 (Suppl 15): 3018–3018. doi: 10.1200/JCO.2020.38.15_suppl.3018.

25. Palaskas N, Lopez-Mattei J, Durand JB et al. Immune checkpoint inhibitor myocarditis: pathophysiological characteristics, diagnosis, and treatment. J Am Heart Assoc 2020; 9 (2): e013757. doi: 10.1161/JAHA.119.013757.

26. Mahmood SS, Fradley MG, Cohen JV et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 2018; 71 (16): 1755–1764. doi: 10.1016/j.jacc.2018.02.037.

27. Escudier M, Cautela J, Malissen N et al. Clinical features, management, and outcomes of immune checkpoint inhibitor-related cardiotoxicity. Circulation 2017; 136 (21): 2085–2087. doi: 10.1161/CIRCULATIONAHA.117.030571.

28. Shelly S, Agmon-Levin N, Altman A et al. Thymoma and autoimmunity. Cell Mol Immunol 2011; 8 (3): 199–202. doi: 10.1038/cmi.2010.74.

29. Suzuki S, Ishikawa N, Konoeda F et al. Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology 2017; 89 (11): 1127–1134. doi: 10.1212/WNL.0000000000004359.

30. 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; 36 (17): 1714–1768. doi: 10.1200/JCO.2017.77.6385.