Cardiovascular Immunotoxicity Associated with Immune Checkpoint Inhibitors in Metastatic Melanoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Registration
2.2. Data Sources, Search Strategy, and Data Extraction
2.3. Outcomes
2.4. Statistical Analysis
3. Results
3.1. Descriptions of Included Studies
3.2. Risk of CVAEs Associated with ICI Exposure and Incidence of CV irAEs with an Increased Risk Associated with ICI Exposure in Melanoma
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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ClinicalTrials.gov Identifier | Study | Study Design | Comparison | Advanced or Metastatic Cancer | Prior Systemic Therapy (%) | Mean Patient Age (years) | Follow up Duration (months) | Number of Patients in the ICI Mono Therapy Group | Number of Patients in the Combination ICI Therapy Group | Number of Patients in the Control Group |
---|---|---|---|---|---|---|---|---|---|---|
NCT00636168 | Eggermont Lancet Oncol. 2015 | Phase 3 RCT | Ipilimumab 10 mg/kg vs. placebo | No | 0 | 51.1 | 32.8 | 471 | - | 474 |
NCT01704287 | Ribas Lancet Oncol. 2015 | Phase 2 RCT | Pembrolizumab 2 or 10 mg/kg vs. chemotherapy (paclitaxel + carboplatin, paclitaxel, carboplatin, dacarbazine or temozolomide) | Yes | 46–50 | 60.1 | 10 | 357 | - | 171 |
NCT01721746 | Weber Lancet Oncol. 2015 | Phase 3 RCT | Nivolumab 3 mg/kg vs. chemotherapy (dacarbazine, or carboplatin + paclitaxel) | Yes | 100 | 59.2 | 8.4 | 268 | - | 102 |
NCT01721772 | Robert N. Engl. J. Med. 2015 | Phase 3 RCT | Nivolumab 3 mg/kg + placebo vs. dacarbazine + placebo | Yes | 16.8 | 62.7 | 5.2 | 206 | - | 205 |
NCT01844505 | Larkin N. Engl. J Med. 2015 | Phase 3 RCT | Nivolumab 3 mg/kg vs. Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg vs. Ipilimumab 3 mg/kg | Yes | 0 | 59.6 | 12.2 | 624 | 313 | - |
NCT01927419 | Postow N. Engl. J. Med. 2015 | Phase 3 RCT | Ipilimumab 3 mg/kg + placebo vs. nivolumab 1 mg/kg + Ipilimumab 3 mg/kg | Yes | 0 | 63.7 | 11 | 46 | 94 | - |
NCT02362594 | Eggermont N. Engl. J. Med. 2018 | Phase 3 RCT | Pembrolizumab 200 mg vs. placebo | No | 0 | 53.8 | 15 | 509 | - | 502 |
NCT02374242 | Long Lancet Oncol. 2018 | Phase 2 RCT | Nivolumab 3 mg/kg vs. Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg | Yes | - | 61.1 | 14 | 25 | 35 |
Immune Checkpoint Inhibitors Arm (n/N) | Control Arm (n/N) | n Study/.I2 | OR (IC95%) | p | |||||
---|---|---|---|---|---|---|---|---|---|
Melanomas | Other Tumors | Melanomas | Other Tumors | Melanomas | Other Tumors | Melanomas | Other Tumors | ||
Supraventricular arrhythmias | 13/1811 | 85/11,217 | 5/1454 | 60/7406 | 5/0% | 29/27% | 1.74 (0.66–4.58) | 0.77 (0.50–1.20) | 0.13 |
Ventricular arrhythmias | 2/777 | 4/2591 | 0/604 | 2/1572 | 2/0% | 6/31% | 5.57 (0.30–103.56) | 1.18 (0.16–8.80) | 0.39 |
Cardiogenic shock | 7/1605 | 60/10,338 | 2/1249 | 27/6873 | 4/0% | 26/0% | 1.88 (0.47–7.58) | 1.45 (0.93–2.24) | 0.73 |
Dyslipidemia | 30/625 | 9/1422 | 0/273 | 2/661 | 2/0% | 2/0% | 4.74 (2.16–10.41) | 1.91 (0.54–6.79) | 0.23 |
Venous thromboembolic events | 15/1811 | 231/12,154 | 10/1454 | 162/8303 | 5/52% | 34/26% | 1.01 (0.30–3.39) | 0.97 (0.74–1.25) | 0.95 |
High blood pressure | 122/1811 | 376/7668 | 87/1454 | 208/4758 | 5/62% | 18/76% | 1.71 (0.86–3.40) | 1.12 (0.74–1.70) | 0.30 |
High pulmonary pressure | 2/2710 | 5/1696 | 6/3% | 0.26 (0.05–1.23) | 0.42 | ||||
Myocardial infarction | 4/1605 | 66/11,093 | 1/1249 | 30/7631 | 3/0% | 28/0% | 2.50 (0.40–15.57) | 1.47 (0.97–2.22) | 0.58 |
Cerebral ischemia | 5/1605 | 93/10,731 | 5/1249 | 36/7454 | 4/0% | 29/0% | 0.59 (0.16–2.16) | 1.68 (1.17–2.40) | 0.13 |
Heart failure | 7/1811 | 82/9903 | 1/1454 | 28/6634 | 5/0% | 27/0% | 3.62 (0.87–15.07) | 1.90 (1.28–2.80) | 0.39 |
Myocarditis | 1/509 | 13/4857 | 0/502 | 1/3587 | 1/NA% | 11/0% | 7.29 (0.14–367.33) | 4.25 (1.44–12.51) | 0.79 |
Pericarditis | 1/357 | 70/8906 | 0/171 | 22/6702 | 1/NA% | 23/2% | 4.39 (0.07–289.28) | 2.17 (1.41–3.32) | 0.74 |
Torsades de pointes/QT prolongation | 1/509 | 2/1211 | 0/502 | 1/589 | 1/NA% | 3/37% | 7.29 (0.14–367.33) | 0.96 (0.05–19.87) | 0.42 |
Conduction disturbance | 1/828 | 2/3004 | 1/645 | 4/1782 | 2/29% | 6/0% | 0.71 (0.02–21.34) | 0.29 (0.05–1.52) | 0.64 |
Valvulopathy | 1/1769 | 2/1363 | 3/41% | 0.37 (0.02–7.64) | 0.39 |
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L’Orphelin, J.-M.; Dollalille, C.; Akroun, J.; Alexandre, J.; Dompmartin, A. Cardiovascular Immunotoxicity Associated with Immune Checkpoint Inhibitors in Metastatic Melanoma. Cancers 2023, 15, 2170. https://doi.org/10.3390/cancers15072170
L’Orphelin J-M, Dollalille C, Akroun J, Alexandre J, Dompmartin A. Cardiovascular Immunotoxicity Associated with Immune Checkpoint Inhibitors in Metastatic Melanoma. Cancers. 2023; 15(7):2170. https://doi.org/10.3390/cancers15072170
Chicago/Turabian StyleL’Orphelin, Jean-Matthieu, Charles Dollalille, Julia Akroun, Joachim Alexandre, and Anne Dompmartin. 2023. "Cardiovascular Immunotoxicity Associated with Immune Checkpoint Inhibitors in Metastatic Melanoma" Cancers 15, no. 7: 2170. https://doi.org/10.3390/cancers15072170