Characteristics of second primary malignancies following bispecific antibodies therapy

Background The risk of secondary primary malignancies (SPMs) associated with bispecific antibody (BsAb)—a promising alternative to chimeric antigen receptor (CAR)-T therapy—remains insufficiently explored.Methods Using large-scale, real-world data from the US Food and Drug Administration’s Adverse E...

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Main Authors: Dan Liu, Tong Li, Liang Wang, Jia Guo, Xinyu Zhou, Hongsheng Zhou, Xiaojie Liang, Baiwei Luo, Bingyu Lin, WeiXiang Lu, Shengyu Tian, Zihong Cai, Zhihao Jin, Keren Chen
Format: Article
Language:English
Published: BMJ Publishing Group 2025-04-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/13/4/e011200.full
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author Dan Liu
Tong Li
Liang Wang
Jia Guo
Xinyu Zhou
Hongsheng Zhou
Xiaojie Liang
Baiwei Luo
Bingyu Lin
WeiXiang Lu
Shengyu Tian
Zihong Cai
Zhihao Jin
Keren Chen
author_facet Dan Liu
Tong Li
Liang Wang
Jia Guo
Xinyu Zhou
Hongsheng Zhou
Xiaojie Liang
Baiwei Luo
Bingyu Lin
WeiXiang Lu
Shengyu Tian
Zihong Cai
Zhihao Jin
Keren Chen
author_sort Dan Liu
collection DOAJ
description Background The risk of secondary primary malignancies (SPMs) associated with bispecific antibody (BsAb)—a promising alternative to chimeric antigen receptor (CAR)-T therapy—remains insufficiently explored.Methods Using large-scale, real-world data from the US Food and Drug Administration’s Adverse Event Reporting System, we identified the relative frequency and characteristics of SPMs following BsAbs therapy and conducted a comprehensive comparison of treatment-related SPM profiles between BsAbs and CAR-T therapies.Results We identified 108 cases among 10,280 BsAb-treated patients. The incidence risk of SPMs was stable over the past 8 years, accounting for 1–2% of all adverse events, with a case fatality rate of 29.63% among the SPM cases. Myeloid leukemias and non-Hodgkin’s lymphoma were more frequent in blinatumomab recipients, while solid malignancies predominated in those treated with teclistamab. Time-to-onset (TTO) was significantly shorter in BsAb recipients compared with non-recipients, with weight and treatment duration influencing TTO, while no significant differences in TTO were observed across different BsAb products, ages, and genders. Our findings highlight the first year of BsAbs as a critical window for early detection and intervention. Although the overall risk of SPMs was lower with BsAbs than with CAR-T, the outcomes of SPMs were comparable in both groups. TTO and SPM patterns were statistically similar between the two therapies.Conclusion Our study provides the first detailed characterization of SPMs post-BsAb, underscoring the need for continued pharmacovigilance and individualized risk management to mitigate SPM risks in patients undergoing BsAb therapy.
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spelling doaj-art-a8db603cbb5c470e9709d85391d5a82c2025-08-20T03:08:06ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-04-0113410.1136/jitc-2024-011200Characteristics of second primary malignancies following bispecific antibodies therapyDan Liu0Tong Li1Liang Wang2Jia Guo3Xinyu Zhou4Hongsheng Zhou5Xiaojie Liang6Baiwei Luo7Bingyu Lin8WeiXiang Lu9Shengyu Tian10Zihong Cai11Zhihao Jin12Keren Chen133 Department of Radiology, Shunde Hospital, Southern Medical University, Foshan, China5 Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China1 Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China1 Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China4 The First School of Clinical Medicine, Guangdong Medical University, Zhanjiang, China2 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China1 Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China2 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China2 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China1 Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China1 Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China2 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China4 The First School of Clinical Medicine, Guangdong Medical University, Zhanjiang, China6 Department of General Medicine, Maoming People’s Hospital, Maoming, ChinaBackground The risk of secondary primary malignancies (SPMs) associated with bispecific antibody (BsAb)—a promising alternative to chimeric antigen receptor (CAR)-T therapy—remains insufficiently explored.Methods Using large-scale, real-world data from the US Food and Drug Administration’s Adverse Event Reporting System, we identified the relative frequency and characteristics of SPMs following BsAbs therapy and conducted a comprehensive comparison of treatment-related SPM profiles between BsAbs and CAR-T therapies.Results We identified 108 cases among 10,280 BsAb-treated patients. The incidence risk of SPMs was stable over the past 8 years, accounting for 1–2% of all adverse events, with a case fatality rate of 29.63% among the SPM cases. Myeloid leukemias and non-Hodgkin’s lymphoma were more frequent in blinatumomab recipients, while solid malignancies predominated in those treated with teclistamab. Time-to-onset (TTO) was significantly shorter in BsAb recipients compared with non-recipients, with weight and treatment duration influencing TTO, while no significant differences in TTO were observed across different BsAb products, ages, and genders. Our findings highlight the first year of BsAbs as a critical window for early detection and intervention. Although the overall risk of SPMs was lower with BsAbs than with CAR-T, the outcomes of SPMs were comparable in both groups. TTO and SPM patterns were statistically similar between the two therapies.Conclusion Our study provides the first detailed characterization of SPMs post-BsAb, underscoring the need for continued pharmacovigilance and individualized risk management to mitigate SPM risks in patients undergoing BsAb therapy.https://jitc.bmj.com/content/13/4/e011200.full
spellingShingle Dan Liu
Tong Li
Liang Wang
Jia Guo
Xinyu Zhou
Hongsheng Zhou
Xiaojie Liang
Baiwei Luo
Bingyu Lin
WeiXiang Lu
Shengyu Tian
Zihong Cai
Zhihao Jin
Keren Chen
Characteristics of second primary malignancies following bispecific antibodies therapy
Journal for ImmunoTherapy of Cancer
title Characteristics of second primary malignancies following bispecific antibodies therapy
title_full Characteristics of second primary malignancies following bispecific antibodies therapy
title_fullStr Characteristics of second primary malignancies following bispecific antibodies therapy
title_full_unstemmed Characteristics of second primary malignancies following bispecific antibodies therapy
title_short Characteristics of second primary malignancies following bispecific antibodies therapy
title_sort characteristics of second primary malignancies following bispecific antibodies therapy
url https://jitc.bmj.com/content/13/4/e011200.full
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