Fatal Case of Immune-Related Myocarditis and Myositis Due to Treatment with Immune Checkpoint and Tyrosine Kinase Inhibitors
DOI:
https://doi.org/10.20344/amp.21306Keywords:
Carcinoma, Renal Cell/drug therapy, Immune Checkpoint Inhibitors/adverse effects, Myocarditis/chemically induced, Myositis/chemically induced, Tyrosine Kinase Inhibitors/adverse effectsAbstract
Immune checkpoint inhibitor and tyrosine kinase inhibitor combinations have become the new standard of care in the first-line treatment of metastatic clear cell renal cell carcinoma. However, there is a growing concern regarding severe immune-related adverse events. A 78-year-old man with metastatic clear cell renal cell carcinoma, treated with pembrolizumab and axitinib, was admitted to the emergency department 30 days after initiating treatment due to rapidly progressive myositis. Myocarditis with severe ventricular dysfunction was identified. Muscular biopsy findings were compatible with inflammatory myopathy associated with immune checkpoint inhibitors. Initial treatment with high-dose corticosteroids showed an insufficient response. Therapeutic escalation on the third day with methylprednisolone, immunoglobulin, and abatacept resulted in clinical improvement. On the eleventh day, a sudden malignant arrhythmia occurred, followed by cardiac arrest. This represents one of the first case reports describing myocarditis and myositis during treatment with pembrolizumab-axitinib. While immune checkpoint inhibitor may play a major role, it is also possible that the tyrosine kinase inhibitor, while attempting to promote immune modulation, also increases severe toxicities.Downloads
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Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384:829-41. DOI: https://doi.org/10.1056/NEJMoa2026982
Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384:1289-300. DOI: https://doi.org/10.1056/NEJMoa2035716
Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1103-15. DOI: https://doi.org/10.1056/NEJMoa1816047
Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116-27. DOI: https://doi.org/10.1056/NEJMoa1816714
Luo YB, Tang W, Zeng Q, Duan W, Li S, Yang X, et al. Case report: the neuromusclar triad of immune checkpoint inhibitors: a case report of myositis, myocarditis, and myasthenia gravis overlap following toripalimab treatment. Front Cardiovasc Med. 2021;8:714460. DOI: https://doi.org/10.3389/fcvm.2021.714460
Jin Y, Xu Z, Yan H, He Q, Y X, Luo P. A comprehensive review of clinical cardiotoxicity incidence of FDA-approved small-molecule kinase inhibitors. Front Pharmacol. 2020;11:891. DOI: https://doi.org/10.3389/fphar.2020.00891
Jin Y, Xu Z, Yan H, He Q, Yang X, Luo P. Combining immune checkpoint inhibition plus tyrosine kinase inhibition as first and subsequent treatments for metastatic renal cell carcinoma. Cancer Med. 2022;11:3106-14. DOI: https://doi.org/10.1002/cam4.4679
Wiest N, Majeed U, Seegobin K, Zhao Y, Lou Y, Manochakian R. Role of immune checkpoint inhibitor therapy in advanced EGFR-mutant non-small cell lung cancer. Front Oncol. 2021;11:751209. DOI: https://doi.org/10.3389/fonc.2021.751209
Oshima Y, Tanimoto T, Yuji K, Tojo A. EGFR-TKI-associated interstitial pneumonitis in nivolumab-treated patients with non-small cell lung cancer. JAMA Oncol. 2018;4:1112-5. DOI: https://doi.org/10.1001/jamaoncol.2017.4526
Schoenfeld AJ, Arbour KC, Rizvi H, Iqbal AN, Gadgeel SM, Girshman J, et al. Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib. Ann Oncol. 2019;30:839-44. DOI: https://doi.org/10.1093/annonc/mdz077
Kotake M, Murakami H, Kenmotsu H, Naito T, Takahashi T. High incidence of interstitial lung disease following practical use of osimertinib in patients who had undergone immediate prior nivolumab therapy. Ann Oncol. 2017;28:669-70. DOI: https://doi.org/10.1093/annonc/mdw647
Chitturi KR, Xu J, Araujo-Gutierrez R, Bhimaraj A, Guha A, Hussain I, et al. Immune checkpoint inhibitor-related adverse cardiovascular events in patients with lung cancer. JACC: CardioOncol. 2019;1:182-92. DOI: https://doi.org/10.1016/j.jaccao.2019.11.013
Guo CW, Alexander M, Dib Y, Lau PK, Weppler AM, Au-Yeung G, et al. A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies. Eur J Cancer. 2020;124:15-24. DOI: https://doi.org/10.1016/j.ejca.2019.09.009
Chen MH, Kerkelä R, Force T. Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circ. 2008;118:84-95. DOI: https://doi.org/10.1161/CIRCULATIONAHA.108.776831
Nguyen LS, Bretagne M, Arrondeau J, Zahr N, Ederhy S, Abbar B, et al. Reversal of immune-checkpoint inhibitor fulminant myocarditis using personalizeddose-adjusted abatacept and ruxolitinib: proof of concept. J Immunother Cancer. 2022;10:004699. DOI: https://doi.org/10.1136/jitc-2022-004699
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