PMID- 32817069
OWN - NLM
STAT- MEDLINE
DCOM- 20210719
LR  - 20240329
IS  - 2059-7029 (Electronic)
IS  - 2059-7029 (Linking)
VI  - 5
IP  - 4
DP  - 2020 Aug
TI  - Mycobacterial infections due to PD-1 and PD-L1 checkpoint inhibitors.
LID - 10.1136/esmoopen-2020-000866 [doi]
LID - e000866
AB  - BACKGROUND: Immune checkpoint inhibitors that block programmed cell death-1 
      (PD-1) and programmed cell death ligand-1 (PD-L1) have improved outcomes for many 
      cancer subtypes but do exhibit toxicity, in the form of immune-related adverse 
      events. OBJECTIVE: The aim of this study was to investigate the emerging 
      toxicities of PD-1 and PD-L1 inhibitors including acute or reactivation of 
      tuberculosis (TB) and atypical mycobacterial infection (AMI). METHODS: This study 
      was completed as a retrospective review using the US Food and Drug Administration 
      Adverse Events Reporting System (FAERS) for incidence of TB and AMI due to PD-1 
      and PD-L1 inhibitors compared with other FDA (Food and Drug Administration) 
      approved drugs. The statistical methods included disproportionality signal 
      analysis using the reporting OR (ROR) to compare cases. The 95% Wald CI was 
      reported to assess the precision of the ROR. RESULTS: Out of the 10 146 481 
      adverse events (AEs) reported to FAERS for all drugs between 1 January 2015 and 
      31 March 2020, 73 886 AEs were due to the five FDA approved PD-1/PD-L1 
      inhibitors. Seventy-two cases of TB were due to PD-1/PD-L1 inhibitors. 
      Specifically, 45 cases (62.5%) due to nivolumab, 18 (25%) due to pembrolizumab, 5 
      (7%) due to atezolizumab and 4 (5.5%) due to durvalumab. There were 13 cases of 
      AMI: 9 (69.3%) due to nivolumab, 2 (15.3%) due to pembrolizumab and 1 (7.7%) each 
      due to durvalumab and atezolizumab. Avelumab was not attributed to any AE of TB 
      or AMI. From analysis of the FAERS database, the calculated ROR for TB due to 
      PD-1/PD-L1 inhibitors was 1.79 (95% CI, 1.42 to 2.26) (p<0.0001) and for AMI was 
      5.49 (95% CI, 3.15 to 9.55) (p<0.0001). CONCLUSION: PD-1/PD-L1 inhibitors used in 
      the treatment of cancer subtypes is associated with increased TB and AMI risk. 
      Although this complication is rare, clinicians using PD-1/PD-L1 inhibitors should 
      be aware of the risks.
CI  - (c) Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No 
      commercial re-use. Published by BMJ on behalf of the European Society for Medical 
      Oncology.
FAU - Anand, Kartik
AU  - Anand K
AUID- ORCID: 0000-0003-4480-1443
AD  - Callahan Cancer Center, Great Plains Health, North Platte, Nebraska, USA 
      kartikanand88@gmail.com.
FAU - Sahu, Geetanjali
AU  - Sahu G
AD  - Creighton University School of Medicine, Omaha, Nebraska, USA.
FAU - Burns, Ethan
AU  - Burns E
AD  - Houston Methodist Hospital, Houston, Texas, USA.
FAU - Ensor, Allyne
AU  - Ensor A
AD  - William Carey University College of Osteopathic Medicine, Hattiesburg, 
      Mississippi, USA.
FAU - Ensor, Joe
AU  - Ensor J
AD  - Houston Methodist Research Institute, Houston, Texas, USA.
FAU - Pingali, Sai Ravi
AU  - Pingali SR
AD  - Houston Methodist Hospital, Houston, Texas, USA.
FAU - Subbiah, Vivek
AU  - Subbiah V
AUID- ORCID: 0000-0002-6064-6837
AD  - Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, 
      UT MD Anderson Cancer Center, Houston, Texas, USA.
FAU - Iyer, Swaminathan P
AU  - Iyer SP
AD  - Department of Lymphoma/Myeloma, Division of Cancer Medicine, UT MD Anderson 
      Cancer Center, Houston, Texas, USA.
LA  - eng
PT  - Journal Article
PL  - England
TA  - ESMO Open
JT  - ESMO open
JID - 101690685
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - B7-H1 Antigen
MH  - Female
MH  - Humans
MH  - Immune Checkpoint Inhibitors/*pharmacology
MH  - Male
MH  - Mycobacterium
MH  - Mycobacterium Infections/*etiology
MH  - Nivolumab
MH  - Programmed Cell Death 1 Receptor
MH  - Retrospective Studies
PMC - PMC7437685
OTO - NOTNLM
OT  - atypical mycobacterial infections
OT  - checkpoint inhibitors
OT  - immune related adverse events
OT  - immunology
OT  - tuberculosis
COIS- Competing interests: VS and SPI COI can be found online.
EDAT- 2020/08/21 06:00
MHDA- 2021/07/20 06:00
PMCR- 2020/08/18
CRDT- 2020/08/21 06:00
PHST- 2020/06/15 00:00 [received]
PHST- 2020/07/04 00:00 [revised]
PHST- 2020/07/08 00:00 [accepted]
PHST- 2020/08/21 06:00 [entrez]
PHST- 2020/08/21 06:00 [pubmed]
PHST- 2021/07/20 06:00 [medline]
PHST- 2020/08/18 00:00 [pmc-release]
AID - S2059-7029(20)32666-1 [pii]
AID - esmoopen-2020-000866 [pii]
AID - 10.1136/esmoopen-2020-000866 [doi]
PST - ppublish
SO  - ESMO Open. 2020 Aug;5(4):e000866. doi: 10.1136/esmoopen-2020-000866.