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.