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 |
---|---|---|---|---|---|---|---|---|---|
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 | 0 | 0 |
Caroline Robert et al., 2014 [12] | Prospective study | III | 418 (210 vs. 208) | Nivolumab vs. Dacarbazine |
3 mg/kg/2 weeks vs. standard dose | 308 (153 vs. 155) | 5 | Hypotension 1 vs. 4 | 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 | 0 | 0 |
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 |
F Stephen Hodi et al., 2016 [15] | Prospective study | II | 142 (95 vs. 47) | Nivolumab + Ipilimumab vs. Ipilimumab + placebo | 1 mg/kg + 3 mg/kg/4 doses/3 weeks vs. 3 mg/kg + placebo/4 doses/3 weeks | 140 (94 vs. 46) | 7 | Hypotension 3 vs. 0; Ventricular arrhythmia 1 vs. 0; Ventricular tachycardia 1 vs. 0; Atrial fibrillation 1 vs. 0; Myocardial infarction 1 vs. 0 | 5 |
Caroline Robert et al., 2015 [16] | Prospective study | III | 834 (278 vs. 277 vs. 256) | Pembrolizumab vs. Pembrolizumab vs. Ipilimumab | 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) | 4 | Hypertension 3 vs. 1 vs. 0 |
2 |
J. Weber, M. et al., 2017 [17] | Prospective study | III | 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 | 0 |
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 |
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 |
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 |
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 |
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 | Dose and Frequency | Non-CAE | CAE | Manifestation | 3–5 Grade CAE |
---|---|---|---|---|---|---|---|---|---|
卡利安R等人,2019[27] | 回顾性研究 | 星期日 | 252 (117 与. 135) | Non-ICI vs. ICI (Nivolumab/Pembrolizumab) Nivolumab (Niv) Pembrolizumab (Pem) |
标准剂量与增加剂量(Niv < 540 mg;540~1440 mg;> 1440 mg Pem < 600 mg;600~1707 mg;>1707 mg) | 星期日 | 93 (42 与. 51) | 心律失常 31 vs. 25;心脏相关胸痛 12 vs. 25;瓣膜性心脏病4 vs. 2;心肌病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 8 | 40(主要 CAE) |
斯科特N等人,2015[28] | 前瞻性研究 | 我 | 129 (33 对 37 对. 59) | 尼沃鲁单抗 | 1 mg/kg vs. 3 mg/kg vs. 10 mg/kg,静脉使用/2 周,8 周周期,最长 96 周。 | 91 (21 与. 25 与. 45) | 0 | 0 | 0 |
Tony S K Mok et al., 2019[29] | 前瞻性研究 | 第三 | 1251 (636 与. 615) | 彭布利珠单抗与铂类化疗 | 200毫克/3周,最多35个周期,而铂类化疗4至6个周期。 | 1112 (515 与. 597) | 1 (1 与 0) | 心肌炎 1 vs. 0 | 1 |
Achim Rittmeyer et al., 2017[30] | 前瞻性研究 | 第三 | 1187 (609 与. 578) | 阿替利珠单抗 vs. 多西他赛 | 1200毫克/3周对比75毫克/米2/3 周 | 886 (390 与. 496) | 0 | 0 | 0 |
S.J. Antonia et al., 2017[31] | 前瞻性研究 | 第三 | 718 (475 与. 234) | 杜瓦鲁单抗 vs. 安慰剂 |
10 毫克/公斤/2 周,最长 12 个月,与 安慰剂相比 |
421 (301 与. 120) | 26 (21 与. 5) | ACS 9 对 2;心律失常 7 对 1;心力衰竭 7 vs. 0;心脏骤停 2 vs. 1;心源性休克1对0;心肌病1 vs. 0;心肌炎 0 vs. 1;心包积液 2 vs. 0 | 星期日 |
石岳全等, 2021[32] | 观察性研究 | 星期日 | 1905 (1162 对 743) (598 对 455 对 273 对 176 对 125 对 81 对 62 对 34 对 23) |
仅 ICI(Pembrolizumab/Nivolumab/Camrelizumab/Treprizumab/Tisilizumab/Atezolizumab/Durvalumab/Ipilimumab)仅与联合治疗 | 至少一剂 | 647 | 22 (22 与. 0) | cTnI 升高或心肌炎 22 | 9 |
Roy S Herbst et al., 2016[33] | 前瞻性研究 | 二/三 | 991 (339 与. 343 与. 309) | 彭布罗利珠单抗 vs. 多西他赛 | Pem 2毫克/千克,Pem 10毫克/千克与多西紫杉醇75毫克/米2/3 周 | 690 (215 与. 225 与. 250) | 1 (0 对 1 对 1) | 心肌梗死 0 对 1 对 0;急性心力衰竭 0 vs. 0 vs. 1 | 1 |
Martin Reck et al., 2016[34] | 前瞻性研究 | 第三 | 304 (154 与. 150) | 彭布利珠单抗与铂 类化疗 |
200 毫克/3 周与标准剂量相比 | 52 (45 与. 7) | 0 | 0 | 0 |
H. Borghaei et al., 2015[35] | 前瞻性研究 | 第三 | 555 (278 与. 268) | 尼沃鲁单抗 vs. 多西他赛 | 3 毫克/千克/2 周对比 75 毫克/米2/3 周 | 432 (196 与. 236) | 3 (3 与. 0) | 心脏压塞 1 vs. 0;心包积液 1 vs. 0 心动过速 1 vs. 0 |
3 |
Julie Brahmer et al., 2015[36] | 前瞻性研究 | 第三 | 272 (135:137) | 尼沃鲁单抗 vs. 多西他赛 | 3 毫克/千克/2 周对比 75 毫克/米2/3周。 | 187 (76 与. 111) | 0 | 0 | 0 |
D.P. Carbone et al., 2017[37] | 前瞻性研究 | 第三 | 530 (267 与. 263) | 尼沃鲁单抗与化疗(铂类) | 3毫克/ kg / 2周与标准剂量相比,六个周期。 | 431 (188 与. 243) | 2 (2 与. 0) | 心肌梗死 1 vs. 0;心包积液恶性 1 vs. 0 | 2 |
This entry is adapted from the peer-reviewed paper 10.3390/jcdd9070203