Cardiovascular toxicities associated with bispecific T-cell engager therapy
Background Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs.Methods Leveraging the US Food and D...
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BMJ Publishing Group
2024-02-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/2/e008518.full |
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| author | Ahmed Sayed Malak Munir Eric H Yang Daniel Addison Sarah Khan Jiwon Kim Syed Mahmood Narendranath Epperla Alexa Meara Sanam M Ghazi Mussammat Ferdousi Satyam Krishan Adnan Shaaban Alma Habib Onaopepo Kola-Kehinde Patrick Ruz Sneha Sharma Stephanie Feldman |
| author_facet | Ahmed Sayed Malak Munir Eric H Yang Daniel Addison Sarah Khan Jiwon Kim Syed Mahmood Narendranath Epperla Alexa Meara Sanam M Ghazi Mussammat Ferdousi Satyam Krishan Adnan Shaaban Alma Habib Onaopepo Kola-Kehinde Patrick Ruz Sneha Sharma Stephanie Feldman |
| author_sort | Ahmed Sayed |
| collection | DOAJ |
| description | Background Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs.Methods Leveraging the US Food and Drug Administration’s Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated.Results From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome.Conclusion In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk. |
| format | Article |
| id | doaj-art-4daf6a6fa2be4e8dbd01f020034d0b6a |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-4daf6a6fa2be4e8dbd01f020034d0b6a2024-11-14T01:15:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-02-0112210.1136/jitc-2023-008518Cardiovascular toxicities associated with bispecific T-cell engager therapyAhmed Sayed0Malak Munir1Eric H Yang2Daniel Addison3Sarah Khan4Jiwon Kim5Syed Mahmood6Narendranath Epperla7Alexa Meara8Sanam M Ghazi9Mussammat Ferdousi10Satyam Krishan11Adnan Shaaban12Alma Habib13Onaopepo Kola-Kehinde14Patrick Ruz15Sneha Sharma16Stephanie Feldman17Ain Shams University Faculty of Medicine, Cairo, EgyptAin Shams University Faculty of Medicine, Cairo, EgyptMedicine, UCLA Medical Center, Los Angeles, California, USAThe Ohio State University Medical Center, Columbus, Ohio, USAThe Ohio State University Medical Center, Columbus, Ohio, USAWeill Cornell Medicine, New York, New York, USACatholic Health Medical Center, New York, New York, USAThe Ohio State University Medical Center, Columbus, Ohio, USAThe Ohio State University Medical Center, Columbus, Ohio, USAThe Ohio State University Medical Center, Columbus, Ohio, USAThe Ohio State University Medical Center, Columbus, Ohio, USAUniversity of Oklahoma Medical Center, City, Oklahoma, USAThe Ohio State University Medical Center, Columbus, Ohio, USAThe Ohio State University Medical Center, Columbus, Ohio, USAThe Ohio State University Medical Center, Columbus, Ohio, USAThe Ohio State University Medical Center, Columbus, Ohio, USAThe Ohio State University Medical Center, Columbus, Ohio, USAWeill Cornell Medicine, New York, New York, USABackground Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs.Methods Leveraging the US Food and Drug Administration’s Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated.Results From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome.Conclusion In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.https://jitc.bmj.com/content/12/2/e008518.full |
| spellingShingle | Ahmed Sayed Malak Munir Eric H Yang Daniel Addison Sarah Khan Jiwon Kim Syed Mahmood Narendranath Epperla Alexa Meara Sanam M Ghazi Mussammat Ferdousi Satyam Krishan Adnan Shaaban Alma Habib Onaopepo Kola-Kehinde Patrick Ruz Sneha Sharma Stephanie Feldman Cardiovascular toxicities associated with bispecific T-cell engager therapy Journal for ImmunoTherapy of Cancer |
| title | Cardiovascular toxicities associated with bispecific T-cell engager therapy |
| title_full | Cardiovascular toxicities associated with bispecific T-cell engager therapy |
| title_fullStr | Cardiovascular toxicities associated with bispecific T-cell engager therapy |
| title_full_unstemmed | Cardiovascular toxicities associated with bispecific T-cell engager therapy |
| title_short | Cardiovascular toxicities associated with bispecific T-cell engager therapy |
| title_sort | cardiovascular toxicities associated with bispecific t cell engager therapy |
| url | https://jitc.bmj.com/content/12/2/e008518.full |
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