DISCUSSION
ICIs have remodeled cancer treatment, and their usage in oncology
continues to expand in extent and usage. In this example, we look at a
patient with NSCLC treated with pembrolizumab, an ICI that works by
blocking the PD-1 receptor on cancer cells. The PD-1 receptor promotes
cancer growth by inhibiting anti-tumor T-cell activity. As a result, ICI
treatment that targets the PD-1 receptor restores the anti-tumor immune
response4,5. However, the malignant cells are not the
only ones affected by this selective targeting of PD-1 receptor
expression. Consequently, it is relatively common for patients receiving
immunotherapy to have an ICI-related adverse event (irAE); nonetheless,
cardiac myocyte-related irAEs are linked with the highest
mortality6. Numerous researches have elaborated on the
cardio-protective effect of PD-1 in mitigating auto-immune mediated
damage targeting cardiac myocytes, and it is thought that PD-1
suppression contributes to ICI-associated myocarditis. Nonetheless, the
pathophysiological underpinnings of immunotherapy-related cardiotoxicity
are unknown, and further study is needed7.
Although reports indicate a 0.1–1% incidence rate of ICI-associated
myocarditis, real incidence is likely underreported due to imprecise
diagnostic tests, varied clinical presentation, and lack of
awareness8. The difficulty of screening and
identifying people at risk for developing an irAE is exacerbated by such
obstacles. Despite these obstacles, individuals with ICI-associated
myocarditis have reported death rates of 25–50% 8.As a result, early detection and diagnosis are critical for reversing
the potentially deadly effects of cardiotoxicity.
The majority of patients report adverse cardiac events occurring 3–6
months after therapy, while delayed immune effects have been recorded up
to 2 years after treatment9. Patients with
ICI-associated myocarditis may present with cardiac symptoms, although
these may be vague and nonspecific6, as in this case
report. While the presenting symptoms of ICI-associated myocarditis
vary, recent research found that approximately 25% of patients may
exhibit myositis symptoms such as muscular weakness, increased creatine
kinase levels, and ptosis6. Because patients are not
routinely checked for myocarditis while on ICI medication, a diagnosis
of ICI-associated myositis necessitates a careful cardiac
examination6. An EKG, troponin measurements, and
echocardiography are proposed as diagnostic tools if anticipated
cardiotoxicity. According to a study of 35 patients with ICI-associated
myocarditis, 89 percent had abnormal EKG findings such as tachycardia,
ST-segment abnormalities, and QT prolongation, among other
abnormalities. On echocardiography, 94% had an elevated troponin level,
51% had a preserved left ventricular ejection fraction (LVEF), and 35%
had profound LV dysfunction10.
Studies advocate discontinuing ICI therapy as soon as possible to
mitigate the toxicity of ICI-associated myocarditis, starting
corticosteroids and immunosuppression8. However, due
to the low frequency of ICI-associated myocarditis, there is a paucity
of relevant research to advise proper treatment. All patients with
ICI-associated myocarditis should have their ICI therapy terminated, and
steroid therapy instituted, with cardiac stability and treatment
response driving further management8.
In extreme situations, further immunosuppressive medications such
infliximab may be required. Mycophenolate mofetil (MMF) or tacrolimus
might be used in individuals who have high-grade myocarditis that is not
responding to steroids8. ICIs may be the only way to
improve overall survival in many patients with NSCLC; nevertheless,
resuming ICI therapy after a myocarditis episode is contentious. For
example, following re-challenge, 55 percent of patients with various
IrAEs acquired a new or recurrent IrAE, according to research by
Simonaggio et al., and the authors advise avoiding re-challenge in the
case of ICI-related myocarditis2. In situations of
mild myocarditis, Ganatra et al. recommend restarting ICI therapy if no
symptoms of recurrence have been seen after one month of monitoring.
Patients without signs of left ventricular dysfunction or troponin
increase are included in this group3.