PMID- 33613286
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210223
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - Graft Versus Host Disease Associated with Immune Checkpoint Inhibitors: A 
      Pharmacovigilance Study and Systematic Literature Review.
PG  - 619649
LID - 10.3389/fphar.2020.619649 [doi]
LID - 619649
AB  - Background: In patients with allogenic hematopoietic stem cell transplantation 
      (allo-HSCT), immune-checkpoint inhibitors (ICI) are used to treat malignancy 
      recurrence. However, ICI are also associated with graft vs. host disease (GVHD). 
      In this pharmacovigilance analysis, we aimed to characterize cases of GVHD 
      associated with ICI, drawn from the World Health Organization pharmacovigilance 
      database, VigiBase(R), and from literature. Methods: We performed VigiBase(R) query 
      of cases of GVHD associated with ICI. These cases were combined with those of 
      literature, not reported in VigiBase(R). The Bayesian estimate of 
      disproportionality analysis, the information component, was considered 
      significant if its 95% credibility interval lower bound was positive; denoting a 
      significant association between GVHD and the suspected ICI. Time to onset between 
      ICI and GVHD onset and subsequent mortality were assessed. Results: 
      Disproportionality analysis yielded 93 cases of GVHD associated with ICI (61.8% 
      men, median age 38 [interquartile range = 27; 50] years). Cases were mostly 
      associated with nivolumab (53/93, 57.0%), pembrolizumab (23/93, 24.7%) and 
      ipilimumab (12/93, 12.9%) monotherapies. GVHD events occurred after 1 [1; 5.5] 
      injection of ICI, with a time to onset of 35 [IQR = 14; 176] days. Immediate 
      subsequent mortality after GVHD was 24/93, 25.8%. There was no significant 
      difference in mortality depending on the molecule (p = 0.41) or the combination 
      regimen (combined vs. monotherapy, p = 0.60). Previous history of GVHD was 
      present in 11/18, 61.1% in cases reported in literature. Conclusion: In this 
      worldwide pharmacovigilance study, disproportionality yielded significant 
      association between GVHD and ICI, with subsequent mortality of 25.8%. Previous 
      history of GVHD was reported in more than half of cases. Clinicaltrials.gov 
      identifier: NCT03492242.
CI  - Copyright (c) 2021 Nguyen, Raia, Lebrun-Vignes and Salem.
FAU - Nguyen, Lee S
AU  - Nguyen LS
AD  - CMC Ambroise Pare, Research and Innovation-RICAP, Neuilly-sur-Seine, France.
AD  - Sorbonne Universite, Clinical Investigations Center Paris-Est, AP.HP.6 
      Pitie-Salpetriere University Hospital, INSERM, Paris, France.
FAU - Raia, Lisa
AU  - Raia L
AD  - Intensive Care Medicine Department, AP.HP.Centre Cochin University Hospital, 
      Paris, France.
FAU - Lebrun-Vignes, Benedicte
AU  - Lebrun-Vignes B
AD  - Sorbonne Universite, Clinical Investigations Center Paris-Est, AP.HP.6 
      Pitie-Salpetriere University Hospital, INSERM, Paris, France.
AD  - Creteil Paris-Est University, EpiderMe, Creteil, France.
FAU - Salem, Joe-Elie
AU  - Salem JE
AD  - Sorbonne Universite, Clinical Investigations Center Paris-Est, AP.HP.6 
      Pitie-Salpetriere University Hospital, INSERM, Paris, France.
AD  - Department of Medicine, Cardio-Oncology Program, Vanderbilt University Medical 
      Center, Nashville, TN, United States.
LA  - eng
SI  - ClinicalTrials.gov/NCT03492242
PT  - Journal Article
DEP - 20210205
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7892442
OTO - NOTNLM
OT  - adverse (side) effects
OT  - graft-versus-host disease
OT  - immunotherapy
OT  - pharmacovigilance
OT  - vigibase(R)
COIS- J-ES has participated to BMS advisory boards. The remaining 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- 2021/02/23 06:00
MHDA- 2021/02/23 06:01
PMCR- 2021/02/05
CRDT- 2021/02/22 05:53
PHST- 2020/10/20 00:00 [received]
PHST- 2020/12/23 00:00 [accepted]
PHST- 2021/02/22 05:53 [entrez]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2021/02/23 06:01 [medline]
PHST- 2021/02/05 00:00 [pmc-release]
AID - 619649 [pii]
AID - 10.3389/fphar.2020.619649 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Feb 5;11:619649. doi: 10.3389/fphar.2020.619649. 
      eCollection 2020.