With immune checkpoint inhibitors, beware of myocarditis! study

Immune checkpoint inhibitors (ICIs) are anti-tumor drugs that have been in clinical use for less than 10 years, and while the efficacy is exciting, other systemic adverse reactions are also attracting increasing attention
.

Recently, Liu Jian, Wang Lan and others of Peking University People's Hospital conducted a retrospective analysis
of patients with myocarditis caused by immune checkpoint inhibitors in the hospital in 2018~2021.

Myocarditis caused by immune checkpoint inhibitors is often manifested as arrhythmia and heart failure, which is prone to liver injury and muscle damage, and the prognosis of severe patients is poor
.

The investigators pointed out that in the near term after the application of immune checkpoint inhibitors, especially within 1 month, adverse cardiovascular events should be closely monitored, and once they occur, glucocorticoid therapy and even gamma globulin should be given in time according to the degree of the patient's condition, in order to prevent and reverse the progression
of the disease at an early stage.

In this study, the investigators searched a total of 4 patients with myocarditis caused by immune checkpoint inhibitors who visited the hospital in 2018~2021 through the case system, of which 3 were females with an age range of 46~83 years old
.

All four patients had an applied cell death protein 1 (PD-1) inhibitor, and one of them received a combination of PD-1 inhibitor and T-cell immunoglobulin/immune receptor tyrosine inhibitory motif-domain protein (TIGIT) monoclonal antibody
.

The onset time after the application of immune checkpoint inhibitors is 17~27d
.

2 patients with heart failure; 3 patients had arrhythmias of varying degrees; One patient had a small pericardial effusion; No patients developed severe valvular heart disease
.

Except for myocarditis, all 4 cases were complicated by liver injury; Three cases were complicated with muscle injury
.

The investigators pointed out that this suggests that immune checkpoint inhibitors myocardial damage often does not exist independently, and is often combined with other system damage, especially liver damage and muscle damage
.

Except for one mild patient who did not receive special treatment, all three patients received glucocorticoids
.

Among them, the patient who combined PD-1 inhibitor + TIGIT monoclonal antibody was also treated with glucocorticoids + intravenous gamma globulin
.

In the end, 3 patients improved significantly after treatment, but patients who combined PD-1 inhibitor + TIGIT monoclonal antibody died
of sustained ventricular tachycardia + cardiogenic shock.

According to reports, adverse cardiovascular events caused by immune checkpoint inhibitors include myocarditis/cardiomyopathy, pericarditis/pericardial effusion, acute myocardial ischemia/coronary artery spasm, valvular lesions and hypertension
.

Scholars from Fuwai Hospital published a review pointing out that the possible mechanism of cardiotoxicity associated with immune checkpoint inhibitors is that immune checkpoint inhibitors activate cytotoxic T lymphocytes, and T cells directly invade cardiomyocytes and cause heart damage
.

Adverse cardiac events associated with immune checkpoint inhibitors
can be relatively more serious or even fatal.

According to the literature, the incidence of myocarditis caused by immune checkpoint inhibitors is 1.
0%~1.
4%, and rises to 2.
4%
if more than 2 immune checkpoint inhibitors are combined.

Once myocarditis caused by immune checkpoint inhibitors occurs, the mortality rate can reach 36.
96%~50.
00%.

The investigator introduced the experience pointed out that for non-mild patients, it is necessary to add hormones in time, especially severe patients, it is necessary to actively add gamma globulin or give hormone shock therapy, otherwise the disease progresses quickly and the prognosis is extremely poor
.