PMID- 35784751
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220829
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Myelodysplastic Syndrome/Acute Myeloid Leukemia Following the Use of Poly-ADP 
      Ribose Polymerase (PARP) Inhibitors: A Real-World Analysis of Postmarketing 
      Surveillance Data.
PG  - 912256
LID - 10.3389/fphar.2022.912256 [doi]
LID - 912256
AB  - Background and purpose: poly-ADP ribose polymerase (PARP) inhibitors show 
      impressive efficacy in a range of tumors. However, concerns about rare and fatal 
      adverse events, including myelodysplastic syndrome (MDS) and acute myelogenous 
      leukemia (AML) have arisen. The aim of this study was to excavate and evaluate 
      the risk of PARP inhibitors causing MDS and AML based on real-world data from two 
      international pharmacovigilance databases. Methods: We analyzed adverse event 
      (AE) reports of four PARP inhibitors (olaparib, niraparib, rucaparib and 
      talazoparib) associated with MDS and AML from the United States Food and Drug 
      Administration (FDA) Adverse Event Reporting System (FAERS) and EudraVigilance 
      (EV) databases between 1 October 2014, and 30 September 2021, including 
      demographic characteristics, fatality and times to onset. Three different data 
      mining algorithms were used to detect the signals of PARP inhibitors associated 
      with MDS and AML. Results: In total, 16,710 and 11,937 PARP inhibitor AE reports 
      were found in the FAERS and EV databases, of which 332 and 349 were associated 
      with MDS and AML, respectively. The median latencies of MDS and AML associated 
      with PARP inhibitors were 211 [interquartile range (IQR) 93.5-491.25] days and 
      355 (IQR 72.00-483.50) days, respectively. The average fatality rates of MDS and 
      AML caused by the four PARP inhibitors were 37.96 and 60.41%, respectively, in 
      the FAERS database, while those in the EV database were 5.83 and 12.16%, 
      respectively. Based on the criteria used for the three algorithms, a significant 
      disproportionate association was found between PARP inhibitors as a drug class 
      and MDS/AML. Notably, the risk of MDS was much higher than that of AML. Olaparib 
      appeared to have a stronger association with MDS and AML than did other PARP 
      inhibitors. Conclusion: In the real world, PARP inhibitors increase the risk of 
      MDS and AML, which can result in high mortality and tend to occur during 
      long-term use. Our findings provide objective evidence for the postmarketing 
      safety of PARP inhibitors.
CI  - Copyright (c) 2022 Zhao, Ma, Fu, Wang, Wang, Chen and Yang.
FAU - Zhao, Quanfeng
AU  - Zhao Q
AD  - Department of Pharmacy, The First Affiliated Hospital of Third Military Medical 
      University (Army Medical University), Chongqing, China.
FAU - Ma, Pan
AU  - Ma P
AD  - Department of Pharmacy, The First Affiliated Hospital of Third Military Medical 
      University (Army Medical University), Chongqing, China.
FAU - Fu, Peishu
AU  - Fu P
AD  - Department of Pharmacy, The First Affiliated Hospital of Third Military Medical 
      University (Army Medical University), Chongqing, China.
FAU - Wang, Jiayu
AU  - Wang J
AD  - Department of Pharmacy, Women and Children's Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Department of Pharmacy, Chongqing Health Center for Women and Children, 
      Chongqing, China.
FAU - Wang, Kejing
AU  - Wang K
AD  - Department of Pharmacy, Women and Children's Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Department of Pharmacy, Chongqing Health Center for Women and Children, 
      Chongqing, China.
FAU - Chen, Lin
AU  - Chen L
AD  - Department of Pharmacy, Women and Children's Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Department of Pharmacy, Chongqing Health Center for Women and Children, 
      Chongqing, China.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Pharmacy, Women and Children's Hospital of Chongqing Medical 
      University, Chongqing, China.
AD  - Department of Pharmacy, Chongqing Health Center for Women and Children, 
      Chongqing, China.
LA  - eng
PT  - Journal Article
DEP - 20220615
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
EIN - Front Pharmacol. 2022 Aug 11;13:990048. PMID: 36034796
PMC - PMC9240214
OTO - NOTNLM
OT  - PARP inhibitors
OT  - acute myeloid leukemia
OT  - myelodysplastic syndrome
OT  - pharmacovigilance
OT  - real-world
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/06 06:00
MHDA- 2022/07/06 06:01
PMCR- 2022/06/15
CRDT- 2022/07/05 10:29
PHST- 2022/04/04 00:00 [received]
PHST- 2022/05/27 00:00 [accepted]
PHST- 2022/07/05 10:29 [entrez]
PHST- 2022/07/06 06:00 [pubmed]
PHST- 2022/07/06 06:01 [medline]
PHST- 2022/06/15 00:00 [pmc-release]
AID - 912256 [pii]
AID - 10.3389/fphar.2022.912256 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Jun 15;13:912256. doi: 10.3389/fphar.2022.912256. 
      eCollection 2022.