PMID- 34050534
OWN - NLM
STAT- MEDLINE
DCOM- 20210929
LR  - 20210929
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Linking)
VI  - 96
IP  - 9
DP  - 2021 Sep 1
TI  - Adverse events reported to the U.S. Food and Drug Administration Adverse Event 
      Reporting System for tisagenlecleucel.
PG  - 1087-1100
LID - 10.1002/ajh.26246 [doi]
AB  - The U.S. Food and Drug Administration (FDA) approved the first chimeric antigen 
      receptor T-cell therapy, tisagenlecleucel, in August 2017. We sought to describe 
      adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS) 
      for tisagenlecleucel in the post-marketing period. We searched FAERS reports to 
      identify U.S. patients treated with tisagenlecleucel between August 30, 
      2017-August 31, 2019. We reviewed individual reports, calculated AE frequencies 
      and reporting rates (RRs), and used Empirical Bayesian Geometric Mean methods to 
      identify disproportionate reporting. We identified 646 de-duplicated reports with 
      a median age at AE of 18 (interquartile range: 11-56) years. The overall RR was 
      81.0%, and more than 95% of reports described a serious outcome. Cytokine release 
      syndrome (CRS) was the most frequently reported AE (51.1%) with a RR of 41.4%; 
      neurotoxicity was reported less frequently (21.2%), with a RR of 17.2%. Most 
      disproportionately reported AEs were listed on the package insert or confounded 
      by indication. We identified 13 subsequent neoplasms (SPN), the majority 
      occurring within 6 months of tisagenlecleucel administration, and none reporting 
      evidence of insertional mutagenesis. A total of 165 reports (26%) described a 
      death outcome; most deaths occurred >30 days after treatment. The majority of 
      deaths (64%) were due to progression of the underlying lymphoid neoplasm, and few 
      (<5%) were attributed to CRS or neurotoxicity. We did not identify new safety 
      concerns reported for tisagenlecleucel in the post-marketing period. Reporting 
      rates for CRS and neurotoxicity were lower than identified in the prelicensure 
      clinical trials.
CI  - Published 2021. This article is a U.S. Government work and is in the public 
      domain in the USA.
FAU - Dores, Graca M
AU  - Dores GM
AUID- ORCID: 0000-0002-3985-2935
AD  - U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, 
      Office of Biostatistics and Epidemiology, Silver Spring, Maryland, USA.
FAU - Jason, Christopher
AU  - Jason C
AD  - U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, 
      Office of Biostatistics and Epidemiology, Silver Spring, Maryland, USA.
FAU - Niu, Manette T
AU  - Niu MT
AUID- ORCID: 0000-0002-3942-2118
AD  - U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, 
      Office of Biostatistics and Epidemiology, Silver Spring, Maryland, USA.
FAU - Perez-Vilar, Silvia
AU  - Perez-Vilar S
AUID- ORCID: 0000-0003-1272-1502
AD  - U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, 
      Office of Biostatistics and Epidemiology, Silver Spring, Maryland, USA.
LA  - eng
PT  - Journal Article
DEP - 20210611
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - Q6C9WHR03O (tisagenlecleucel)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Adverse Drug Reaction Reporting Systems
MH  - Aged
MH  - Child
MH  - Female
MH  - Humans
MH  - Immunotherapy, Adoptive/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Product Surveillance, Postmarketing
MH  - Receptors, Antigen, T-Cell/*therapeutic use
MH  - United States
MH  - United States Food and Drug Administration
MH  - Young Adult
EDAT- 2021/05/30 06:00
MHDA- 2021/09/30 06:00
CRDT- 2021/05/29 06:21
PHST- 2021/05/15 00:00 [received]
PHST- 2021/05/18 00:00 [accepted]
PHST- 2021/05/30 06:00 [pubmed]
PHST- 2021/09/30 06:00 [medline]
PHST- 2021/05/29 06:21 [entrez]
AID - 10.1002/ajh.26246 [doi]
PST - ppublish
SO  - Am J Hematol. 2021 Sep 1;96(9):1087-1100. doi: 10.1002/ajh.26246. Epub 2021 Jun 
      11.