Chimeric Antigen Receptor T-Cell Therapy for Cancer and Heart

COVID-19 Illness and Heart Failure

“…Because respiratory disease is established in the setting of COVID-19, characteristically, acute respiratory distress syndrome is also accompanied by pulmonary edema, as noted in post-mortem studies (3). In later stages of COVID-19 illness, a hyperinflammatory state is manifest that is akin to a cytokine release syndrome as described in response to cancer therapy as noted with immune checkpoint inhibition and T-cell-engaging therapies such as chimeric antigen receptor T cells (11). This multisystemic syndrome results in elevated cytokines and dysregulated T cells with lymphopenia (typically an Check for evidence of hyperinflammation or a cytokine release storm (elevated troponin, natriuretic peptides, CRP, and serum ferritin of >1,000 ng/ml (measure IL-6 levels if available) If cardiac function is reduced (LVEF <0.50%), consider supportive care with inotropic therapy but move to consider anticytokine therapy with drugs such as tocilizumab and corticosteroids Note that therapy in COVID-19 remains experimental.…”

Cardiotoxicity of Contemporary Anticancer Immunotherapy

“…Cytokine release syndrome (CRS) is a frequent adverse effect of CAR T cell therapy, which consists of a constellation of signs and symptoms caused by supraphysiologic levels of inflammatory cytokines released by the activated CAR T cells and other immune cells such as macrophages [ 8 ••]. Cardiotoxicity in the form of myocardial injury, as evident by troponin elevation, cardiomyopathy or heart failure development, arrhythmia, capillary leak syndrome, and circulatory collapse, are mostly reported in the context of high-grade CRS [ 38 ].…”

“…Although CRS is reported to occur fairly frequently (70–90%), the toxic effects mediated by cytokine release are typically mild in severity. However, 10–20% of patients can develop life-threatening complications such as vascular leak syndrome with circulatory collapse and multiorgan failure [ 8 ••, 12 , 42 ]. In pivotal studies involving 287 patients, cardiac arrest was reported in 4 patients and cardiac failure in 2 patients, likely underestimating the true incidence and impact of cardiotoxicity associated with CAR T cell therapy [ 3 – 5 ].…”

“…Contemporary immunotherapy, such as immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell therapy, has dramatically improved outcomes for a wide variety of cancers with an otherwise poor prognosis [ 1 – 5 ]. However, both of these therapies can potentially lead to serious cardiovascular adverse effects [ 6 , 7 , 8 ••]. As the use of immunotherapy expands for the treatment of patients with a wide variety of malignancies and preexisting cardiovascular disease or risk factors, such cardiotoxicity will be observed more frequently.…”

“…Moreover, there is growing enthusiasm to explore the utility of genetically engineered T cells in the treatment of autoimmune disease and infections [ 11 ]. However, CAR T cell therapy is associated with potentially life-threatening cytokine release syndrome (CRS), which in turn may lead to arrhythmia, myocardial injury, cardiomyopathy, and cardiovascular collapse [ 8 ••, 12 ]. Although insults related to CRS toxicity might be transient and reversible in most instances in patients with adequate cardiovascular reserve, they can be particularly challenging in higher risk, often elderly, patients with preexisting cardiovascular disease.…”