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Hematological toxicities in immune checkpoint inhibitors: A pharmacovigilance study from 2014 to 2019
Author(s) -
Ye Xiaofei,
Hu Fangyuan,
Zhai Yinghong,
Qin Yingyi,
Xu Jinfang,
Guo Xiaojing,
Zhuang Yonglong,
He Jia
Publication year - 2020
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.2743
Subject(s) - medicine , pharmacovigilance , adverse event reporting system , adverse effect , odds ratio , confidence interval , meddra , oncology , pharmacology
Immune checkpoint inhibitors (ICIs) have shown remarkable clinical effects in many cancer types. However, ICIs could also induce severe organ system toxicities, including those of the hematological system. The present study aimed to extensively characterize the hematological toxicities of ICIs immunotherapy. Data were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1, 2014, to March 31, 2019. Disproportionality analysis, including information component (IC) and reporting odds ratio (ROR), was used to detect potential disproportionality signal. The lower boundary of the 95% confidence interval of IC (IC 025 ) exceeding zero or that of ROR (ROR 025 ) exceeding one was considered statistically significant for detecting disproportionality signal. A total of 29 294 335 records were extracted from the database, with 132 573 related to ICIs. Overall, hematological adverse events (AEs) were more frequently reported in ICIs (IC 025 : 0.81; ROR 025 : 1.80). On further analysis, hematological AEs were overreported in female patients (female vs male, ROR 025 : 1.04) and anti‐CTLA‐4 monotherapy groups (anti‐CTLA‐4 vs anti‐PD‐1, ROR 025 : 1.33) and polytherapy groups (polytherapy vs monotherapy, ROR: 1.20, ROR 025 : 1.11). Moreover, class‐specific hematological AEs were also detected and differed in unique ICI regimens. Notably, disseminated intravascular coagulation had the highest proportion of death outcomes among the top 10 most frequently reported ICI‐associated hematological AEs. Our study shows a high reporting frequency of hematological AEs induced by ICI monotherapy (especially by anti‐CTLA‐4 therapy) and reinforced by polytherapy. A spectrum of class‐specific disproportionality signal was also detected; some were fatal and reported for the first time. The heterogeneous clinical spectrum of hematological toxicities, including the non‐negligible proportion of death as reported outcome, are warranted to be reminded by clinicians. Early recognition and management of ICI‐related hematological AEs are highly important and further studies are needed to confirm the results of our study.