Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study
Introduction: Immune checkpoint inhibitors (ICIs) have substantially improved the clinical outcomes of various malignancies. However, the adverse event of tumor lysis syndrome (TLS) has not been included in the National Comprehensive Cancer Network guidelines or drug inserts. In this study, we aimed...
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Frontiers Media S.A.
2021-09-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.679207/full |
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| author | Li Wang Xiaolin Li Xiaolin Li Bin Zhao Dan Mei Jiandong Jiang Jingli Duan |
| author_facet | Li Wang Xiaolin Li Xiaolin Li Bin Zhao Dan Mei Jiandong Jiang Jingli Duan |
| author_sort | Li Wang |
| collection | DOAJ |
| description | Introduction: Immune checkpoint inhibitors (ICIs) have substantially improved the clinical outcomes of various malignancies. However, the adverse event of tumor lysis syndrome (TLS) has not been included in the National Comprehensive Cancer Network guidelines or drug inserts. In this study, we aimed to establish the relationship between ICI therapies and TLS events using data from a real-world pharmacovigilance database.Methods: The MedDRA terms of TLS and both generic and brand names of ICIs were retrieved from the FDA Adverse Event Reporting System. Four frequentist algorithms were employed to confirm the association between the TLS and the ICI regimens, involving anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA-4), anti–programmed death receptor-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1), and anti-(CTLA-4 + PD-1). A descriptive and statistical analysis was performed according to the case information.Results: One hundred sixty-four TLS cases, where patients underwent anti-CTLA-4 (n = 14), anti-(PD-1)/(PD-L1) (n = 113), or anti-(CTLA-4 + PD-1) (n = 37) therapies, were collected between the first quarter of 2004 and the fourth quarter of 2020. The most coverage-reporting year, age-group, sex, reporter, region, country, and indication were 2020 (n = 62), 60–74 years (n = 65), males (n = 105), physician (n = 66), Asia (n = 80), Japan (n = 67), and lung and thymus malignancies (n = 40), respectively. The median TLS onset time associated with anti-CTLA-4, anti-(PD-1)/(PD-L1), and anti-(CTLA-4 + PD-1) therapies was 6 (IQR: 2–39.5), 9 (IQR: 2–40), and 20 (IQR: 7.5–37.75) days, respectively. Mortality distribution of 71 reported death outcomes among three groups was statistically significant. All four algorithm signal values of anti-(CTLA-4 + PD-1) were higher than those of anti-CTLA-4 and anti-(PD-1)/(PD-L1).Conclusion: Elderly male patients with lung and thymus malignancies are frequently predisposed to TLS. ICI therapies could induce TLS in both solid and hematological malignancies. The rapid onset time and poor outcomes of patients prompt caution from health-care professionals. |
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| format | Article |
| id | doaj.art-62ac41dafdff43f4a8acbb8674064168 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T00:40:48Z |
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| spelling | doaj.art-62ac41dafdff43f4a8acbb86740641682022-12-21T18:44:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.679207679207Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance StudyLi Wang0Xiaolin Li1Xiaolin Li2Bin Zhao3Dan Mei4Jiandong Jiang5Jingli Duan6Department of Pharmacy, Peking University International Hospital, Beijing, ChinaDepartment of Pharmacy, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Pharmacy, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Pharmacy, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Pharmacy, Peking University International Hospital, Beijing, ChinaIntroduction: Immune checkpoint inhibitors (ICIs) have substantially improved the clinical outcomes of various malignancies. However, the adverse event of tumor lysis syndrome (TLS) has not been included in the National Comprehensive Cancer Network guidelines or drug inserts. In this study, we aimed to establish the relationship between ICI therapies and TLS events using data from a real-world pharmacovigilance database.Methods: The MedDRA terms of TLS and both generic and brand names of ICIs were retrieved from the FDA Adverse Event Reporting System. Four frequentist algorithms were employed to confirm the association between the TLS and the ICI regimens, involving anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA-4), anti–programmed death receptor-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1), and anti-(CTLA-4 + PD-1). A descriptive and statistical analysis was performed according to the case information.Results: One hundred sixty-four TLS cases, where patients underwent anti-CTLA-4 (n = 14), anti-(PD-1)/(PD-L1) (n = 113), or anti-(CTLA-4 + PD-1) (n = 37) therapies, were collected between the first quarter of 2004 and the fourth quarter of 2020. The most coverage-reporting year, age-group, sex, reporter, region, country, and indication were 2020 (n = 62), 60–74 years (n = 65), males (n = 105), physician (n = 66), Asia (n = 80), Japan (n = 67), and lung and thymus malignancies (n = 40), respectively. The median TLS onset time associated with anti-CTLA-4, anti-(PD-1)/(PD-L1), and anti-(CTLA-4 + PD-1) therapies was 6 (IQR: 2–39.5), 9 (IQR: 2–40), and 20 (IQR: 7.5–37.75) days, respectively. Mortality distribution of 71 reported death outcomes among three groups was statistically significant. All four algorithm signal values of anti-(CTLA-4 + PD-1) were higher than those of anti-CTLA-4 and anti-(PD-1)/(PD-L1).Conclusion: Elderly male patients with lung and thymus malignancies are frequently predisposed to TLS. ICI therapies could induce TLS in both solid and hematological malignancies. The rapid onset time and poor outcomes of patients prompt caution from health-care professionals.https://www.frontiersin.org/articles/10.3389/fphar.2021.679207/fullimmune checkpoint inhibitortumor lysis syndromecytotoxic T lymphocyte antigen-4programmed death receptor-1programmed cell death 1 ligand 1pharmacovigilance |
| spellingShingle | Li Wang Xiaolin Li Xiaolin Li Bin Zhao Dan Mei Jiandong Jiang Jingli Duan Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study Frontiers in Pharmacology immune checkpoint inhibitor tumor lysis syndrome cytotoxic T lymphocyte antigen-4 programmed death receptor-1 programmed cell death 1 ligand 1 pharmacovigilance |
| title | Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study |
| title_full | Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study |
| title_fullStr | Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study |
| title_full_unstemmed | Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study |
| title_short | Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study |
| title_sort | immune checkpoint inhibitor associated tumor lysis syndrome a real world pharmacovigilance study |
| topic | immune checkpoint inhibitor tumor lysis syndrome cytotoxic T lymphocyte antigen-4 programmed death receptor-1 programmed cell death 1 ligand 1 pharmacovigilance |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.679207/full |
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