Immune Checkpoint Inhibitors-Related Cardiotoxicity.
CTLA-4 Antigen
/ antagonists & inhibitors
Cardiology
/ methods
Cardiotoxicity
/ diagnosis
Humans
Immune Checkpoint Inhibitors
/ adverse effects
Incidence
Medical Oncology
/ methods
Neoplasms
/ drug therapy
Practice Guidelines as Topic
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Risk Assessment
/ methods
Risk Factors
Severity of Illness Index
Journal
American journal of therapeutics
ISSN: 1536-3686
Titre abrégé: Am J Ther
Pays: United States
ID NLM: 9441347
Informations de publication
Date de publication:
Historique:
pubmed:
23
4
2019
medline:
3
8
2021
entrez:
23
4
2019
Statut:
ppublish
Résumé
Immunotherapy is a significant breakthrough in cancer therapy in the last decade. Immunotherapy is better tolerated compared with chemotherapy. However, it does have side effects, and one of the rare and serious side effects of immunotherapy is cardiotoxicity. Cardiotoxicity has been described with other cancer-related treatments such as chemotherapy and targeted therapy. A high index of suspicion is required, and prompt management with immunosuppression needs to be instituted as soon as possible to prevent fatal outcomes. Research is still ongoing to identify biomarkers that will help us to choose the patients, who will respond well to immunotherapy. Tumor-infiltrating lymphocytes, tumor PD-L1 expression, and tumor mutational burden explored as potential biomarkers. There are no predictive biomarkers to identify patients who are at higher risk of severe cardiotoxicity. Both cardiologists and oncologists should be aware of cardiac toxicity from immune checkpoint inhibitors. All patients who are starting immune checkpoint inhibitors should undergo baseline cardiac risk factor assessment with referral to a cardiologist in a patient with multiple risk factors or previous history of cardiovascular disease. Cardiac immune-related adverse events are higher in patients taking combination therapy with anti-CTLA-4/anti-PD-1 agents compared with monotherapy. Patients with known cardiac comorbidities require a higher level of vigilance to monitor for cardiac toxicity because nonspecific symptoms can lead to rapid clinical deterioration and a higher rate of mortality when treated with checkpoint inhibitors.
Sections du résumé
BACKGROUND
BACKGROUND
Immunotherapy is a significant breakthrough in cancer therapy in the last decade. Immunotherapy is better tolerated compared with chemotherapy. However, it does have side effects, and one of the rare and serious side effects of immunotherapy is cardiotoxicity. Cardiotoxicity has been described with other cancer-related treatments such as chemotherapy and targeted therapy. A high index of suspicion is required, and prompt management with immunosuppression needs to be instituted as soon as possible to prevent fatal outcomes.
AREAS OF UNCERTAINTY
UNASSIGNED
Research is still ongoing to identify biomarkers that will help us to choose the patients, who will respond well to immunotherapy. Tumor-infiltrating lymphocytes, tumor PD-L1 expression, and tumor mutational burden explored as potential biomarkers. There are no predictive biomarkers to identify patients who are at higher risk of severe cardiotoxicity. Both cardiologists and oncologists should be aware of cardiac toxicity from immune checkpoint inhibitors.
CONCLUSION
CONCLUSIONS
All patients who are starting immune checkpoint inhibitors should undergo baseline cardiac risk factor assessment with referral to a cardiologist in a patient with multiple risk factors or previous history of cardiovascular disease. Cardiac immune-related adverse events are higher in patients taking combination therapy with anti-CTLA-4/anti-PD-1 agents compared with monotherapy. Patients with known cardiac comorbidities require a higher level of vigilance to monitor for cardiac toxicity because nonspecific symptoms can lead to rapid clinical deterioration and a higher rate of mortality when treated with checkpoint inhibitors.
Identifiants
pubmed: 31008763
doi: 10.1097/MJT.0000000000000988
pii: 00045391-202012000-00004
doi:
Substances chimiques
CTLA-4 Antigen
0
CTLA4 protein, human
0
Immune Checkpoint Inhibitors
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e591-e598Références
Available at: https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm279174.htm. Accessed March 8, 2019.
Available at: https:wayback.archive-it.org/7993/20170111064250/http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm. Accessed March 8, 2019.
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–264.
Ghatalia P, Zibelman M, Geynisman DM, et al. Approved checkpoint inhibitors in bladder cancer: which drug should be used when? Ther Adv Med Oncol. 2018;10:1758835918788310.
Spencer KR, Wang J, Silk AW, et al. Biomarkers for immunotherapy: current developments and challenges. Am Soc Clin Oncol Educ book. 2016;36:e493–e503.
Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291:319–322.
Grabie N, Gotsman I, DaCosta R, et al. Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8+ T-cell mediated injury in the heart. Circulation. 2007;116:2062–2071.
Lucas JA, Menke J, Rabacal WA, et al. Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice. J Immunol. 2008;181:2513–2521.
Wang J, Okazaki IM, Yoshida T, et al. PD-1 deficiency results in the development of fatal myocarditis in MRL mice. Int Immunol. 2010;22:443–452.
Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270:985–988.
Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375:1749–1755.
Läubli H, Balmelli C, Bossard M, et al. Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma. J Immunother Cancer. 2015;3:11.
Tadokoro T, Keshino E, Makiyama A, et al. Acute lymphocytic myocarditis with anti-PD-1 antibody nivolumab. Circ Heart Fail. 2016;9:e003514.
Hu YB, Zhang Q, Li HJ, et al. Evaluation of rare but severe immune related adverse effects in PD-1 and PD-L1 inhibitors in non-small cell lung cancer: a meta-analysis. Transl Lung Cancer Res. 2017;6(suppl 1):S8–S20.
Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. 2016;13:473–486.
Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev. 2016;45:7–18.
Costa R, Carneiro BA, Agulnik M, et al. Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Oncotarget. 2017;8:8910–8920.
Naidoo J, Page DB, Li BT, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26:2375–2391.
Geisler BP, Raad RA, Esaian D, et al. Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome. J Immunother Cancer. 2015;3:4.
Nghiem PT, Bhatia S, Lipson EJ, et al. PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma. N Engl J Med. 2016;374:2542–2552.
Heinzerling L, Ott PA, Hodi FS, et al. Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy. J Immunother Cancer. 2016;4:50.
Escudier M, Cautela J, Malissen N, et al. Clinical features, management, and outcomes of immune checkpoint inhibitor-related cardiotoxicity. Circulation. 2017;136:2085–2087.
Moslehi JJ, Salem JE, Sosman JA, et al. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018;391:933.
Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018;71:1755–1764.
Voskens CJ, Goldinger SM, Loquai C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS One. 2013;8:e53745.
Roth ME, Muluneh B, Jensen BC, et al. Left ventricular dysfunction after treatment with ipilimumab for metastatic melanoma. Am J Ther. 2016;23:e1925–e1928.
Lyon AR, Yousaf N, Battisti NM, et al. Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol. 2018;19:e447–e458.
Cooper LT. Myocarditis. N Engl J Med. 2009;360:1526–1538.
Lurz P, Eitel I, Adam J, et al. Diagnostic performance of CMR imaging compared with EMB in patients with suspected myocarditis. JACC Cardiovasc Imaging. 2012;5:513–524.
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 Immunother Cancer. 2017;5:95.
Atkins MB, Larkin J. Immunotherapy combined or sequenced with targeted therapy in the treatment of solid tumors: current perspectives. J Natl Cancer Inst. 2016;108:djv414.
Smyth MJ, Ngiow SF, Ribas A, et al. Combination cancer immunotherapies tailored to the tumour microenvironment. Nat Rev Clin Oncol. 2016;13:143–158.
Jain D, Ahmad T, Cairo M, et al. Cardiotoxicity of cancer chemotherapy: identification, prevention and treatment. Ann Transl Med. 2017;5:348.
Johnson DB, Sullivan RJ, Menzies AM. Immune checkpoint inhibitors in challenging populations. Cancer. 2017;123:1904–1911.
Marin-Acevedo JA, Dholaria B, Soyano AE, et al. Next generation of immune checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol. 2018;11:39.