Cardiac Adverse Events in Patients Receiving Immune Checkpoint Inhibitors in the Adjuvant Setting: An FDA Pooled Analysis
ABSTRACT Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. By releasing blocks (checkpoints) on the immune system, they elicit powerful antitumor effects. Despite improving survival, ICIs are associated with serious cardiac toxicities. Previous reports have focused...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Annals of Noninvasive Electrocardiology |
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| Online Access: | https://doi.org/10.1111/anec.70087 |
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| author | Asma Dilawari Mori J. Krantz Ilynn Bulatao Hee‐Koung Joeng Marc Neilson Suparna Wedam Xin Gao Mallorie H. Fiero Abhilasha Nair Marc Theoret Laleh Amiri‐Kordestani |
| author_facet | Asma Dilawari Mori J. Krantz Ilynn Bulatao Hee‐Koung Joeng Marc Neilson Suparna Wedam Xin Gao Mallorie H. Fiero Abhilasha Nair Marc Theoret Laleh Amiri‐Kordestani |
| author_sort | Asma Dilawari |
| collection | DOAJ |
| description | ABSTRACT Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. By releasing blocks (checkpoints) on the immune system, they elicit powerful antitumor effects. Despite improving survival, ICIs are associated with serious cardiac toxicities. Previous reports have focused on advanced cancer; cardiotoxicity data are therefore limited in the curative setting. We evaluated ICI cardiotoxicity in the non‐metastatic setting, where long‐term cardiac safety is a growing public health concern. Methods ICIs approved in the adjuvant setting were pooled and trials with combination chemotherapy were excluded. Cardiac adverse events (AEs) and emerging cardio‐metabolic risks (hyperglycemia, weight gain, hypothyroidism) were assessed. The relative risk (RR) of cardiotoxicity was assessed. Results Ten randomized controlled trials of atezolizumab, ipilimumab, nivolumab, and pembrolizumab in multiple solid tumors were evaluated; among 9244 patients, 5338 received ICIs. No trial performed routine cardiac monitoring. Six percent of ICI patients vs. 4.6% in placebo (RR 1.24, 95% CI 1.04, 1.49) had a cardiac AE and 13 (0.2%) of ICI patients experienced a fatal cardiac AE (RR 4.76, 95% CI 1.07, 21.06). Older age and male sex were associated with a higher risk for cardiac fatality. Arrhythmia was the most common cardiac AE; hypothyroidism was more frequent (14% vs. 2.5%) among ICI‐treated patients. Conclusion This is the largest pooled analysis of cardiac AEs associated with ICIs in the adjuvant setting. Despite no formalized testing for subclinical cardiotoxicity, ICI treatment increased cardiac AEs. These findings are relevant for long‐term cancer survivors, clinicians, and particularly in new drug development, where cardiotoxicity may be substantially underestimated. |
| format | Article |
| id | doaj-art-2c1ff6aa1e5f45e28ef413e507993d09 |
| institution | Kabale University |
| issn | 1082-720X 1542-474X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Noninvasive Electrocardiology |
| spelling | doaj-art-2c1ff6aa1e5f45e28ef413e507993d092025-08-20T03:48:23ZengWileyAnnals of Noninvasive Electrocardiology1082-720X1542-474X2025-05-01303n/an/a10.1111/anec.70087Cardiac Adverse Events in Patients Receiving Immune Checkpoint Inhibitors in the Adjuvant Setting: An FDA Pooled AnalysisAsma Dilawari0Mori J. Krantz1Ilynn Bulatao2Hee‐Koung Joeng3Marc Neilson4Suparna Wedam5Xin Gao6Mallorie H. Fiero7Abhilasha Nair8Marc Theoret9Laleh Amiri‐Kordestani10Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USACenter for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USACenter for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USACenter for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USAOncology Center of Excellence (OCE) U.S. Food and Drug Administration Silver Spring Maryland USACenter for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USACenter for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USACenter for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USACenter for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USACenter for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USACenter for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration Silver Spring Maryland USAABSTRACT Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. By releasing blocks (checkpoints) on the immune system, they elicit powerful antitumor effects. Despite improving survival, ICIs are associated with serious cardiac toxicities. Previous reports have focused on advanced cancer; cardiotoxicity data are therefore limited in the curative setting. We evaluated ICI cardiotoxicity in the non‐metastatic setting, where long‐term cardiac safety is a growing public health concern. Methods ICIs approved in the adjuvant setting were pooled and trials with combination chemotherapy were excluded. Cardiac adverse events (AEs) and emerging cardio‐metabolic risks (hyperglycemia, weight gain, hypothyroidism) were assessed. The relative risk (RR) of cardiotoxicity was assessed. Results Ten randomized controlled trials of atezolizumab, ipilimumab, nivolumab, and pembrolizumab in multiple solid tumors were evaluated; among 9244 patients, 5338 received ICIs. No trial performed routine cardiac monitoring. Six percent of ICI patients vs. 4.6% in placebo (RR 1.24, 95% CI 1.04, 1.49) had a cardiac AE and 13 (0.2%) of ICI patients experienced a fatal cardiac AE (RR 4.76, 95% CI 1.07, 21.06). Older age and male sex were associated with a higher risk for cardiac fatality. Arrhythmia was the most common cardiac AE; hypothyroidism was more frequent (14% vs. 2.5%) among ICI‐treated patients. Conclusion This is the largest pooled analysis of cardiac AEs associated with ICIs in the adjuvant setting. Despite no formalized testing for subclinical cardiotoxicity, ICI treatment increased cardiac AEs. These findings are relevant for long‐term cancer survivors, clinicians, and particularly in new drug development, where cardiotoxicity may be substantially underestimated.https://doi.org/10.1111/anec.70087adjuvantcancercardio oncologycardiotoxicityimmune checkpoint inhibitorsimmunotherapy |
| spellingShingle | Asma Dilawari Mori J. Krantz Ilynn Bulatao Hee‐Koung Joeng Marc Neilson Suparna Wedam Xin Gao Mallorie H. Fiero Abhilasha Nair Marc Theoret Laleh Amiri‐Kordestani Cardiac Adverse Events in Patients Receiving Immune Checkpoint Inhibitors in the Adjuvant Setting: An FDA Pooled Analysis Annals of Noninvasive Electrocardiology adjuvant cancer cardio oncology cardiotoxicity immune checkpoint inhibitors immunotherapy |
| title | Cardiac Adverse Events in Patients Receiving Immune Checkpoint Inhibitors in the Adjuvant Setting: An FDA Pooled Analysis |
| title_full | Cardiac Adverse Events in Patients Receiving Immune Checkpoint Inhibitors in the Adjuvant Setting: An FDA Pooled Analysis |
| title_fullStr | Cardiac Adverse Events in Patients Receiving Immune Checkpoint Inhibitors in the Adjuvant Setting: An FDA Pooled Analysis |
| title_full_unstemmed | Cardiac Adverse Events in Patients Receiving Immune Checkpoint Inhibitors in the Adjuvant Setting: An FDA Pooled Analysis |
| title_short | Cardiac Adverse Events in Patients Receiving Immune Checkpoint Inhibitors in the Adjuvant Setting: An FDA Pooled Analysis |
| title_sort | cardiac adverse events in patients receiving immune checkpoint inhibitors in the adjuvant setting an fda pooled analysis |
| topic | adjuvant cancer cardio oncology cardiotoxicity immune checkpoint inhibitors immunotherapy |
| url | https://doi.org/10.1111/anec.70087 |
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