TY - JOUR
T1 - Cardiotoxicity of fda-approved immune checkpoint inhibitors
T2 - A rare but serious adverse event
AU - Zarifa, Abdulrazzak
AU - Salih, Mohammed
AU - Lopez-Mattei, Juan
AU - Lee, Hun Ju
AU - Iliescu, Cezar
AU - Hassan, Saamir
AU - Palaskas, Nicolas
AU - Durand, Jean Bernard
AU - Mouhayar, Elie
AU - Kim, Joseph
AU - Kim, Peter
N1 - Publisher Copyright:
© 2018 Journal of Immunotherapy and Precision Oncology.
PY - 2018
Y1 - 2018
N2 - Refractory cancer represents a challenge for oncologists in providing treatment options without excessive toxicity and has led to the investigation of immune mechanisms. Immune checkpoint inhibitors (ICIs) directly interfere with the tumor cells' ability to evade the innate and adaptive immune system by targeting specific proteins such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death protein-ligand 1 (PD-L1), which are involved as negative regulators of T-cell function. Their growing success has led to the investigation for frontline treatment in several types of cancers. Even though these ICIs have demonstrated efficacy in the treatment of a variety of cancers, their use has been associated with the development of rare but severe adverse events. These events are the result of targeting specific checkpoint proteins on normal cells of the body as well as secondary downstream off-target effects on normal tissue. Similar to combined conventional cancer treatment, treating with combined ICIs are also associated with a higher risk of adverse events. Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant heart failure, hemodynamic instability, and cardiac arrest. Oncologists must carefully weigh the risk versus the therapeutic benefit of these agents in determining the best option for improving overall survival and minimizing morbidity and mortality of their patients. Our review focuses on the approved ICIs, their mechanism of action, their oncologic efficacy, and the associated potential for cardiovascular toxicity.
AB - Refractory cancer represents a challenge for oncologists in providing treatment options without excessive toxicity and has led to the investigation of immune mechanisms. Immune checkpoint inhibitors (ICIs) directly interfere with the tumor cells' ability to evade the innate and adaptive immune system by targeting specific proteins such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death protein-ligand 1 (PD-L1), which are involved as negative regulators of T-cell function. Their growing success has led to the investigation for frontline treatment in several types of cancers. Even though these ICIs have demonstrated efficacy in the treatment of a variety of cancers, their use has been associated with the development of rare but severe adverse events. These events are the result of targeting specific checkpoint proteins on normal cells of the body as well as secondary downstream off-target effects on normal tissue. Similar to combined conventional cancer treatment, treating with combined ICIs are also associated with a higher risk of adverse events. Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant heart failure, hemodynamic instability, and cardiac arrest. Oncologists must carefully weigh the risk versus the therapeutic benefit of these agents in determining the best option for improving overall survival and minimizing morbidity and mortality of their patients. Our review focuses on the approved ICIs, their mechanism of action, their oncologic efficacy, and the associated potential for cardiovascular toxicity.
KW - Anti-CTLA4
KW - Anti-PD1
KW - Anti-PDL1
KW - Cardiotoxicity
KW - Immune checkpoint inhibitors
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U2 - 10.4103/JIPO.JIPO_15_18
DO - 10.4103/JIPO.JIPO_15_18
M3 - Review article
AN - SCOPUS:85079904421
SN - 2666-2345
VL - 1
SP - 68
EP - 77
JO - Journal of Immunotherapy and Precision Oncology
JF - Journal of Immunotherapy and Precision Oncology
IS - 2
ER -