PMID- 32383782
OWN - NLM
STAT- MEDLINE
DCOM- 20201102
LR  - 20201102
IS  - 1099-1069 (Electronic)
IS  - 0278-0232 (Linking)
VI  - 38
IP  - 4
DP  - 2020 Oct
TI  - Hematological toxicities in immune checkpoint inhibitors: A pharmacovigilance 
      study from 2014 to 2019.
PG  - 565-575
LID - 10.1002/hon.2743 [doi]
AB  - 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.
CI  - (c) 2020 John Wiley & Sons Ltd.
FAU - Ye, Xiaofei
AU  - Ye X
AD  - Department of Health Statistics, Second Military Medical University, Shanghai, 
      China.
FAU - Hu, Fangyuan
AU  - Hu F
AD  - Department of Health Statistics, Second Military Medical University, Shanghai, 
      China.
FAU - Zhai, Yinghong
AU  - Zhai Y
AD  - Department of Health Statistics, Second Military Medical University, Shanghai, 
      China.
AD  - Tongji University School of Medicine, Shanghai, China.
FAU - Qin, Yingyi
AU  - Qin Y
AD  - Department of Health Statistics, Second Military Medical University, Shanghai, 
      China.
FAU - Xu, Jinfang
AU  - Xu J
AD  - Department of Health Statistics, Second Military Medical University, Shanghai, 
      China.
FAU - Guo, Xiaojing
AU  - Guo X
AD  - Department of Health Statistics, Second Military Medical University, Shanghai, 
      China.
FAU - Zhuang, Yonglong
AU  - Zhuang Y
AD  - Beijing Bioknow Information Technology Co.Ltd., Beijing, China.
FAU - He, Jia
AU  - He J
AD  - Department of Health Statistics, Second Military Medical University, Shanghai, 
      China.
AD  - Tongji University School of Medicine, Shanghai, China.
LA  - eng
GR  - 15GWZK0901/Fourth Round of Three-year Action Plan on Public Health Discipline and 
      Talent Program: Evidence-based Public Health and Health Economics/
GR  - 81703296/National Nature Science Foundation of China/
GR  - 2017ZX09304030/National Science and Technology Major Project/
GR  - 2017ZX09304016/National Thirteenth Five Year Plan Major Special Project/
GR  - 18ZR1449500/Nature Science Foundation of Shanghai/
GR  - 2018YQ47/Shanghai municipal commission of health and family planning fund for 
      excellent young scholars/
PT  - Journal Article
DEP - 20200609
PL  - England
TA  - Hematol Oncol
JT  - Hematological oncology
JID - 8307268
RN  - 0 (Antineoplastic Agents, Immunological)
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents, Immunological/*adverse effects
MH  - *Databases, Factual
MH  - Female
MH  - Follow-Up Studies
MH  - Hematologic Diseases/*chemically induced/pathology
MH  - Humans
MH  - Immunotherapy/*adverse effects
MH  - Male
MH  - Neoplasms/*drug therapy/immunology/pathology
MH  - Pharmacovigilance
MH  - Prognosis
MH  - Retrospective Studies
MH  - Survival Rate
MH  - Time Factors
OTO - NOTNLM
OT  - FAERS database
OT  - disproportionality analysis
OT  - hematological toxicity
OT  - immune checkpoint inhibitors
OT  - pharmacovigilance study
EDAT- 2020/05/10 06:00
MHDA- 2020/11/03 06:00
CRDT- 2020/05/09 06:00
PHST- 2019/10/28 00:00 [received]
PHST- 2020/05/01 00:00 [revised]
PHST- 2020/05/03 00:00 [accepted]
PHST- 2020/05/10 06:00 [pubmed]
PHST- 2020/11/03 06:00 [medline]
PHST- 2020/05/09 06:00 [entrez]
AID - 10.1002/hon.2743 [doi]
PST - ppublish
SO  - Hematol Oncol. 2020 Oct;38(4):565-575. doi: 10.1002/hon.2743. Epub 2020 Jun 9.