ICIs-Related Cardiotoxicity in Different Types of Cancer: Comparison
Please note this is a comparison between Version 3 by Sirius Huang and Version 2 by Ting Yu.

Immune checkpoint inhibitors (ICIs), antibodies that target the checkpoints in immune cells, work to activate inhibited T-cells and other cells of the innate and adaptive arms, resulting in the robust activation of the immune system and productive antitumor immune responses. However, ICIs-related cardiotoxicity has been recognized as a rare but fatal consequence. Although there has been extensive research based on different types of ICIs, these studies have not indicated whether cardiotoxicity is specific to a type of cancer.

  • immune checkpoint inhibitors
  • cardiotoxicity
  • cardio-oncology
  • cancer-type-specific

1. Introduction

Cardiovascular disease (CVD) and cancer are global health issues with high morbidity and mortality [1], and numerous studies suggest that there is an overlap in epidemiology, risk factors, and pathophysiologic processes (Figure 1) .
Figure 1. (a) Risk factors for CVD and cancer; (b) Common pathophysiologic processes of CVD and cancer.
With the widespread application of anticancer drugs, the survival of patients has significantly improved, but the related cardiotoxicity affects long-term therapeutic outcomes, and this has attracted considerable attention. Immune checkpoint inhibitors (ICIs), antibodies that target the checkpoints in immune cells, work to activate inhibited T-cells and other cells of the innate and adaptive arms, resulting in the robust activation of the immune system and productive antitumor immune responses. This new type of immunotherapy drug has significantly improved the survival of cancer patients [2][3][4]. However, their use is associated with adverse side effects involving different organs [5][6]. ICIs-related cardiotoxicity, which may develop even without a history of significant cardiac risk factors, includes myocarditis, pericarditis, heart failure, arrhythmias, and vasculitis [7]. In reported cases of adverse ICIs-related events, 6.2% were cardiac adverse events (CAEs), which can be the main determinants of quality of life and increased mortality [8][9][10]

2. Cardiotoxicity in Melanoma

In 16 studies, 24 of 6710 patients on ICIs [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] developed CAEs. This corresponded with an incidence of 0.20–4.93% in which grade 3–5 CAEs accounted for 41.7%. Commonly encountered cardiotoxicities included hypertension (50%), hypotension (16.7%), and myocarditis (8.3%). Treatment-related hypertension was linked to the application of lambrolizumab (58.3%) (PD-1). Nivolumab may have had a correlation with ICIs-related hypotension. Patients treated with a higher dose of ipilimumab, particularly 10 mg/kg × 4 doses/3 weeks, were more prone to fatal adverse events such as cardiac arrest (Table 1).
Table 1. Cardiotoxicity in melanoma.
A total of 11 studies [27][28][29][30][31][32][33][34][35][36][37] included 5404 patients on ICIs, and 101 developed CAEs for an incidence of 0.15–37.78% in which grade 3–5 CAEs accounted for 55.4%. Commonly encountered cardiotoxicities included arrhythmia (32.7%), cardiac-related chest pain (24.8%), elevated cTnI or myocarditis (23.8%), cardiomyopathy (20.8%), pericardial disease (11.9%), and acute coronary syndrome (10.9%). One study indicated that major adverse cardiovascular events (MACEs) were dose-independent of nivolumab and pembrolizumab in lung cancer patients [27]. Those treated with a higher dose of durvalumab, particularly 10 mg/kg × 4 doses/2 weeks, were more prone to fatal adverse events such as a cardiac arrest and cardiogenic shock [31]. One patient treated with pembrolizumab at 10 mg/kg for 3 weeks underwent a myocardial infarction, which led to death (Table 2) [33].
Author, Year Study Type Phase Sample Size Drug
/
kg / 2周与标准剂量相比,六个周期。
2 weeks vs. standard dose for six cycles.
431
(
188
与. 243)
vs. 243)
2 (2 与. 0)vs. 0) 心肌梗死Myocardial infarction 1 vs. 0;心包积液恶性 Pericardial effusion malignant 1 vs. 0 2
 

4. 肾细胞癌的心脏毒性Renal Cell Carcinoma

在七项研究中In seven studies [3848][3949][4050][4151][4252][4353][4454]包括 comprising 1971名ICIs肾细胞癌患者,14名开发CAE,发病率为0.20-2.19%,其中3-5级CAE占35.7%。常见的心脏毒性包括高血压(85.7%)和心肌炎(7.1%)。治疗相关的高血压与纳武鲁单抗加伊匹利单抗治疗(100%)有关。与黑色素瘤和肺癌相比,ICI治疗在肾细胞癌中引起轻度心脏毒性。未发现致命的 CAE。 patients with renal cell carcinomas on ICIs, 14 developed CAEs with an incidence of 0.20–2.19% in which grade 3–5 CAEs accounted for 35.7%. Commonly encountered cardiotoxicities included hypertension (85.7%) and myocarditis (7.1%). Treatment-related hypertension was linked to a nivolumab plus ipilimumab therapy (100%). Compared with melanomas and lung cancer, the ICI therapy caused mild cardiotoxicity in renal cell carcinomas. Fatal CAEs were not found.

5. 尿路上皮癌的心脏毒性Urothelial Carcinoma

在七项研究中In Seven studies [4555][4656][4757][4858][4959][5060][5161]在接受ICI治疗的 111 of 2550名尿路上皮癌患者中,有111例发展为CAE,发病率为0.22- patients with urothelial carcinomas on ICIs developed CAEs with an incidence of 0.22–10.60%,其中3-5级CAE占52.3%。常见的心脏毒性包括高血压(28.8%),心律失常(14.4%)和低血压(6.3%)。血压的波动与阿替珠单抗治疗有关。21例患者出现高血压,7例患者应用 in which grade 3–5 CAEs accounted for 52.3%. Commonly encountered cardiotoxicities included hypertension (28.8%), arrhythmia (14.4%) and hypotension (6.3%). The fluctuation of blood pressure was linked to treatment with atezolizumab. Hypertension was observed in 21 patients and hypotension was observed in 7 after application of atezolizumab后出现低血压。用200. Patients treated with 200 mg pembrolizumab治疗3周(最多35个周期)或每3周以1200mg治疗的患者更容易发生致命的不良事件,如心脏骤停。 for 3 weeks (maximum 35 cycles) or at 1200 mg every three weeks were more prone to fatal adverse events such as a cardiac arrest.

6. 其他类型癌症的心脏毒性Other Types of Cancer

在血液系统恶性肿瘤中,最常遇到的与The most commonly encountered ICIs相关的心脏毒性类型是高血压-related type of cardiotoxicity in hematological malignancies was hypertension [5262][5363][5464][5565].在其他癌症中,如肝细胞癌和恶性胸膜间皮瘤,相关研究并未提出很多病例。 In other cancers, such as hepatocellular carcinomas and malignant pleural mesotheliomas, the relevant research did not present many cases [5666][5767][5868][5969][6070][6171];这些几乎都是心肌炎的病例报告 these were almost all case reports of myocarditis [6272][6373][6474].

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