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.
Author, Year | Study Type | Phase | Sample Size | Drug | Dose and Frequency | Non-CAE | CAE | Manifestation | 3–5 Grade CAE | ||||||||||
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Dose and Frequency | Non-CAE | CAE | Manifestation | 3–5 Grade CAE | |||||||||||||||
Omid Hamid et al., 2017 [11] | Prospective study | II | 528 (178 vs. 179 vs. 171) | Pembrolizumab vs. Pembrolizumab vs. chemotherapy | 2 mg/kg/3 weeks vs. 10 mg/kg/3 weeks vs. standard dose | 528 | 0 | ||||||||||||
卡利安Kalyan R等人, et al., 2019 [2737] | 回顾性研究Retrospective study | 星期日NR | 252 ((117 与. 135) | 0 | vs. 135) | Non-ICI vs. ICI ((Nivolumab/Pembrolizumab)) Nivolumab ((Niv)) Pembrolizumab ( | 0 | ||||||||||||
( | Pem | ) | ) | 标准剂量与增加剂量( | Standard dose vs. increasing dose (Niv < 540 mg; 540~1440 mg; > 1440 mg Pem < 600 mg; 600~1707 mg; >1707 mg)) | 星期日NR | 93 ((42 与. 51)vs. 51) | 心律失常Arrhythmia 31 vs. 25;心脏相关胸痛 Cardiac-related chest pain 12 vs. 25;瓣膜性心脏病 Valvular heart disease 4 vs. 2;心肌病 Cardiomyopathy 13 vs. 20;心包疾病11;心包疾病8;心肌炎1;瓣膜病2;静脉动脉血栓栓塞事件 Myopericardial disease 11; Pericardial disease 8; Myocarditis 1; Valvular-disease 2; Venous arterial thromboembolic events 8 | 40(主要 (major CAE)) | Caroline Robert et al., 2014 [12] | |||||||||
斯科特Scott N等人, et al., 2015 | Prospective study | [III | 418 (210 vs. 208) | 2838]Nivolumab vs. Dacarbazine |
3 mg/kg/2 weeks vs. standard dose | 308 (153 vs. 155) | 5 | Hypotension 1 vs. 4 | 前瞻性研究Prospective study (NSCLC)0 | ||||||||||
我 | I | 129 | ((33 对 37 对. 59)vs. 37 vs. 59) | 尼沃鲁单抗Nivolumab | 1 mg/kg vs. 3 mg/kg vs. 10 mg/kg,静脉使用 intravenously/2 周,8 周周期,最长 96 周。weeks in 8-week cycles for up to 96 weeks. | 91 ((21 与. 25 与. 45)vs. 25 vs. 45) | 0 | 0 | 0 | Jeffrey S Weber et al., 2015 [13] | Prospective study | III | 370 (268 vs. 102) | Nivolumab vs. ICC (Dacarbazine al) | 3 mg/kg/2 weeks vs. standard dose | 362 (181 vs. 81) | 0 | ||
Tony S K Mok et al. | 0 | ,, 2019 [2939] | 前瞻性研究Prospective study (NSCLC) | 第三III | 1251 ((636 与. 615)vs. 615) | 彭布利珠单抗与铂类化疗 | 0 | ||||||||||||
Pembrolizumab vs. platinum-based chemotherapy | 200 | 毫克 | mg | /3 | 周,最多35个周期,而铂类化疗4至6个周期。 weeks for up to 35 cycles vs. platinum-based chemotherapy for four to six cycles. | 1112 ((515 与. 597)vs. 597) | 1 ((1 与 0)vs. 0) | 心肌炎Myocarditis 1 vs. 0 | 1 | Paolo A Ascierto et al., 2017 [14] | Prospective study | III | 726 (364 vs. 362) | Ipilimumab | 10 mg/kg/4 doses/3 weeks vs. 3 mg/kg/4 doses/3 weeks | 514 (286 vs. 228) | 3 | Hypertension 1 vs. 0; Heart arrest 1 vs. 0; Pericarditis 1 vs. 0 | 3 |
Achim Rittmeyer et al.,, 2017 [3040] | 前瞻性研究Prospective study (NSCLC) | 第三III | 1187 ((609 与. 578)vs. 578) | 阿替利珠单抗Atezolizumab vs. 多西他赛Docetaxel | 1200毫克 mg/3周对比75毫克/米 weeks vs. 75 mg/m2/3 周weeks | 886 ((390 与. 496)vs. 496) | 0 | 0 | 0 | F Stephen Hodi et al., 2016 [15] | Prospective study | II | 142 (95 vs. 47) | Nivolumab + Ipilimumab vs. Ipilimumab + placebo | |||||
S.J. Antonia et al.,, 2017 [3141] | 前瞻性研究Prospective study (NSCLC) | 1 mg/kg + 3 mg/kg/4 doses/3 weeks vs. 3 mg/kg + placebo/4 doses/3 weeks | 140 (94 vs. 46) | 7 | 第三III | 718 ((475 与. 234)vs. 234) | 杜瓦鲁单抗Durvalumab vs. | Hypotension 3 vs. 0; Ventricular arrhythmia 1 vs. 0; Ventricular tachycardia 1 vs. 0; Atrial fibrillation 1 vs. 0; Myocardial infarction 1 vs. 0 | 安慰剂Placebo |
10 毫克mg/公斤/2 周,最长kg/2 weeks for up to 12 个月,与months vs. 安慰剂相比placebo5 |
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421 | ( | ( | 301 | 与. 120) | vs. 120) | 26 | ((21 与. 5)vs. 5) | ACS 9 对vs. 2;心律失常 7 对 1;心力衰竭 Arrhythmia 7 vs. 1; Heart failure 7 vs. 0;心脏骤停 Cardiac arrest 2 vs. 1;心源性休克1对0;心肌病 Cardiogenic shock 1 vs. 0; Cardiomyopathy 1 vs. 0;心肌炎 Myocarditis 0 vs. 1;心包积液 Pericardial effusion 2 vs. 0 | 星期日NR | Caroline Robert et al., 2015 [16] | Prospective study | III | |||||||
石岳全等,Yuequan Shi et al., 2021 [3242 | 834 (278 vs. 277 vs. 256) | ] | 观察性研究Observational study (NSCLC/SCLC) | 星期日NR | 1905 ((1162 对 743)vs. 743) ((598 Pembrolizumab vs. Pembrolizumab vs. Ipilimumab |
对 455 对 273 对 176 对 125 对 81 对 62 对 34 对 23)10 mg/kg/2 weeks/doses vs. 10 mg/kg/3 weeks/ doses vs. 3 mg/kg/3 weeks/4 doses | 610 (221 vs. 202 vs. 187) | vs. 455 vs. 273 vs. 176 vs. 125 vs. 81 vs. 62 vs. 34 vs. 23)4 | Hypertension 3 vs. 1 vs. 0 |
2 | |||||||||
仅 | ICI | ( | ( | Pembrolizumab/Nivolumab/Camrelizumab/Treprizumab/Tisilizumab/Atezolizumab/Durvalumab/Ipilimumab)仅与联合治疗) only vs. combination therapy | 至少一剂at least one dose | 647 | 22 ((22 与. 0)vs. 0) | Elevated cTnI 升高或心肌炎 or myocarditis 22 | 9 | J. Weber, M. et al., 2017 [17] | Prospective study | III | |||||||
Roy S Herbst et al., | 906 (453 vs. 453) | Nivolumab vs. Ipilimumab | 3 mg/kg/4 doses/2 weeks vs. 10 mg/kg/4 doses/3 weeks | 884 (438 vs. 446) | 0 | 0 | , 2016 | 0 | |||||||||||
[3343] | 前瞻性研究Prospective study (NSCLC) | 二II/三III | 991 ((339 与vs. 343 与. 309)vs. 309) | 彭布罗利珠单抗Pembrolizumab vs. 多西他赛Docetaxel | Pem 2毫克 mg/千克,kg, Pem 10毫克/千克与多西紫杉醇75毫克/米 mg/kg vs. Docetaxel 75 mg/m2/3 周weeks | 690 ((215 与vs. 225 与. 250)vs. 250) | 1 ((0 对 1 对 1)vs. 1 vs. 1) | 心肌梗死Myocardial infarction 0 对 1 对 0;急性心力衰竭vs. 1 vs. 0; Acute cardiac failure 0 vs. 0 vs. 1 | 1 | J.D. Wolchok et al., 2017 [18] | Prospective study | III | 937 (313 vs. 313 vs. 311) | Nivolumab + Ipilimumab vs. Nivolumab + p vs. Ipilimumab + p p(placebo) |
1 mg/kg+3 mg/kg /3 weeks/4 doses vs. 3 mg/kg/2 weeks + placebo vs. 3 mg/kg/3 weeks/4 doses + placebo |
847 (300 vs. 279 vs. 268) | 0 | 0 | 0 |
Martin Reck et al.,, 2016 [3444] | Jedd D Wolchok et al., 2010 [19] | Prospective study | II | 217 (73 vs. 72 vs. 72) | Ipilimumab | 10 mg/kg vs. 3 mg/kg vs. 0.3 mg/kg/3 weeks/4 doses | 115 (50 vs. 46 vs. 19) | 0 | 0 | 0 | |||||||||
前瞻性研究 | Ines Pires da Silva et al., 2021 [20] | Retrospective study | NR (Not Reported) | 355 (193 vs. 162) | Ipilimumab + Nivolumab/Pembrolizumab/Atezolizumab vs. Ipilimumab | 3 mg/kg/3 weeks/4 doses + standard dose vs. 3 mg/kg/3 weeks/4 doses | 287 (163 vs. 124) | 1 (0 vs. 1) | Myocarditis 0 vs. 1 | 1 | |||||||||
周。 | weeks. | 187 | ( | ( | 76 | 与. 111)vs. 111) | 0 | Patrick Schöffski et al., 2022 [21] | Retrospective study | I/II | 255 (134 vs. 121) | LAG-3 inhibitor Ieramilimab vs. Ieramilimab + Spartalizumab |
Ieramilimab (escalating 1–15 mg/kg)/2 weeks or once/4 weeks vs. Ieramilimab + Spartalizumab q2w or q3w or q4w or Ieramilimab q2w + Spartalizumab q4w | 159 (75 vs. 84) | 0 | 0 | 0 | ||
Alexander M.M. et al., 2020 [22] | Prospective study | III | 1011 (509 vs. 502) | Pembrolizumab vs. placebo | 200 mg/3 weeks for 18 doses | 235 (190 vs. 45) | 1 (1 vs. 0) | Myocarditis 1 vs. 0 | NR | ||||||||||
Prospective study (NSCLC) | 第三 | III | 304 ((154 与. 150)vs. 150) | 彭布利珠单抗与铂Pembrolizumab vs. platinum-based 类化疗chemotherapy |
200 毫克mg/3 周与标准剂量相比 weeks vs. standard dose | 52 ((45 与. 7)vs. 7) | 0 | 0 | 0 | ||||||||||
H. Borghaei et al.,, 2015 [3545] | 前瞻性研究Prospective study (NSCLC) | 第三III | 555 ((278 与. 268)vs. 268) | 尼沃鲁单抗Nivolumab vs. 多西他赛Docetaxel | 3 毫克mg/千克/2 周对比 75 毫克/米kg/2 weeks vs. 75 mg/m2/3 周weeks | 432 ((196 与. 236)vs. 236) | 3 ((3 与. 0)vs. 0) | 心脏压塞Cardiac tamponade 1 vs. 0;心包积液 Pericardial effusion 1 vs. 0 心动过速Tachycardia 1 vs. 0 |
3 | ||||||||||
Julie Brahmer et al.,, 2015 [3646] | 前瞻性研究Prospective study (NSCLC) | 第三III | 272 (135:137) | 尼沃鲁单抗Nivolumab vs. 多西他赛Docetaxel | 3 毫克mg/千克/2 周对比 75 毫克/米kg/2 weeks vs. 75 mg/m2/3 | 0 | 0 | ||||||||||||
D.P. Carbone et al.,, 2017 [3747] | 前瞻性研究Prospective study (NSCLC) | 第三III | 530 ((267 与. 263)vs. 263) | 尼沃鲁单抗与化疗(铂类)Nivolumab vs. Chemotherapy(platinum-based) | 3毫克 mg/kg | Omid Hamid et al., 2013 [23] | Prospective study | I | 135 (57 vs. 56 vs. 22) | Lambrolizumab | 10 mg/kg/2 weeks vs. 10 mg/kg/3 weeks vs. 2 mg/kg/3 weeks | 132 (55 vs. 55 vs. 22) | 7 (2 vs. 4 vs. 1) | Hypertension (2 vs. 4 vs. 1) | NR | ||||
Margaret K. et al., 2018 [24] | Retrospective study | I | 94 (53 vs. 41) | Ipilimumab + Nivolumab Nivolumab (Niv) Ipilimumab (Ipi) |
Niv+Ipi(escalating doses)/3 weeks for four doses, followed by Niv 3 weeks for four doses, then Niv + Ipi/12 weeks for eight doses vs. Niv 1 mg/kg + Ipi 3 mg/kg/3 weeks for 4 doses, followed by Niv 3 mg/kg/2 weeks |
87 | 0 | 0 | 0 | ||||||||||
Ulrich Keilholz et al., 2019 [25] | Prospective study | I | 51 | Avelumab | 10 mg/kg for one-hour intravenous infusion/2 weeks | 39 | 0 | 0 | 0 | ||||||||||
Hussein A et al., 2022 [26] | Retrospective study | II-III | 714 (355 vs. 359) | Relatlimab + Nivolumab vs. Nivolumab | Relatlimab 160 mg + Nivolumab 480 mg vs. Nivolumab 480 mg | 504 (288 vs. 216) | 0 | 0 | 0 |
Author, Year | Study Type | Phase | Sample Size | Drug | |||||
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/ | |||||||||
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 |