PMID- 35906791
OWN - NLM
STAT- MEDLINE
DCOM- 20220920
LR  - 20230106
IS  - 1365-2710 (Electronic)
IS  - 0269-4727 (Print)
IS  - 0269-4727 (Linking)
VI  - 47
IP  - 9
DP  - 2022 Sep
TI  - The pharmacology of blinatumomab: state of the art on pharmacodynamics, 
      pharmacokinetics, adverse drug reactions and evaluation in clinical trials.
PG  - 1337-1351
LID - 10.1111/jcpt.13741 [doi]
AB  - WHAT IS KNOWN AND OBJECTIVE: Bispecific drugs (BDs) belong to the family of 
      immunotherapies along with checkpoint inhibitors and CAR-T cells. In the field of 
      oncology, BDs are designed to simultaneously bind a tumour antigen on the one 
      side and an antigen present on the surface of effector cells on the other. This 
      review summarizes the information available to date on the first marketed 
      BiTE-format bispecific antibody, blinatumomab BLINCYTO(R) in acute lymphoblastic 
      leukaemia. METHODS: A literature search was conducted in the PubMed database by 
      including studies published in English using the term blinatumomab. Furthermore, 
      bibliographies of selected references were also evaluated for relevant articles. 
      Clinical trial (CT) data were retrieved from clinicaltrials.gov (ongoing trials, 
      adverse events [AEs]) and global pharmacovigilance data were retrieved from 
      VigiBase(R). RESULTS AND DISCUSSION: Blinatumomab is a fusion protein which 
      consists of two single-chain variable fragments arranged in tandem: the first 
      binds the CD19 surface antigen of all B cells and the second targets the CD3 
      antigen of T cells. Binding of blinatumomab to B and T cells induces apoptosis of 
      B cells after secretion of granzymes and perforins by T cells. T-cell activation 
      results in secretion of pro-inflammatory cytokines and upregulation of activation 
      markers and adhesion molecules on the surface of T cells. The major CTs that led 
      to an indication show increased overall survival with blinatumomab with better 
      efficacy in patients in haematological remission with minimal residual disease 
      >/=10(-3) . The major AEs are cytokine release syndrome, neurotoxicity and 
      hypogammaglobulinemia. The three most frequent system organ classes in CTs are 
      haematological, gastrointestinal and general disorders. These results are also 
      found in VigiBase(R) but neurological disorders and infections appear more 
      frequently in real life. WHAT IS NEW AND CONCLUSION: This review summarizes the 
      current knowledge of blinatumomab in the literature. The subject of many CTs is 
      to improve the route of administration and expand the indications for treatment.
CI  - (c) 2022 The Authors. Journal of Clinical Pharmacy and Therapeutics published by 
      John Wiley & Sons Ltd.
FAU - Mocquot, Pauline
AU  - Mocquot P
AUID- ORCID: 0000-0001-7181-3525
AD  - Departement de Pharmacologie Medicale, CHU de Toulouse, Universite Toulouse III - 
      Paul Sabatier, Toulouse, France.
FAU - Mossazadeh, Yasmine
AU  - Mossazadeh Y
AD  - Departement de Pharmacologie Medicale, CHU de Toulouse, Universite Toulouse III - 
      Paul Sabatier, Toulouse, France.
FAU - Lapierre, Leopoldine
AU  - Lapierre L
AD  - Departement d'Hematologie et de Medecine Interne, Institut Universitaire du 
      Cancer-Oncopole, CHU de Toulouse, Toulouse, France.
FAU - Pineau, Fanny
AU  - Pineau F
AD  - Departement d'Hematologie et de Medecine Interne, Institut Universitaire du 
      Cancer-Oncopole, CHU de Toulouse, Toulouse, France.
FAU - Despas, Fabien
AU  - Despas F
AUID- ORCID: 0000-0002-3116-9963
AD  - Departement de Pharmacologie Medicale, CHU de Toulouse, Universite Toulouse III - 
      Paul Sabatier, Toulouse, France.
AD  - Universite Toulouse III - Paul Sabatier, Toulouse, France.
AD  - INSERM CIC1436 CIC Toulouse, France.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220729
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (Antigens, CD19)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CD3 Complex)
RN  - 0 (Cytokines)
RN  - 0 (Single-Chain Antibodies)
RN  - 4FR53SIF3A (blinatumomab)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - *Antibodies, Bispecific/adverse effects
MH  - Antigens, CD19
MH  - Antigens, Neoplasm
MH  - *Antineoplastic Agents/adverse effects
MH  - CD3 Complex
MH  - Cytokines
MH  - *Drug-Related Side Effects and Adverse Reactions/drug therapy
MH  - Granzymes
MH  - Humans
MH  - *Single-Chain Antibodies
PMC - PMC9796714
OTO - NOTNLM
OT  - acute lymphoblastic leukaemia
OT  - bispecific antibody
OT  - blinatumomab
OT  - pharmacovigilance
COIS- The authors report no financial relationships or conflict of interests regarding 
      the content herein.
EDAT- 2022/07/31 06:00
MHDA- 2022/09/21 06:00
PMCR- 2022/12/28
CRDT- 2022/07/30 02:42
PHST- 2022/06/27 00:00 [revised]
PHST- 2022/06/14 00:00 [received]
PHST- 2022/06/29 00:00 [accepted]
PHST- 2022/07/31 06:00 [pubmed]
PHST- 2022/09/21 06:00 [medline]
PHST- 2022/07/30 02:42 [entrez]
PHST- 2022/12/28 00:00 [pmc-release]
AID - JCPT13741 [pii]
AID - 10.1111/jcpt.13741 [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2022 Sep;47(9):1337-1351. doi: 10.1111/jcpt.13741. Epub 2022 
      Jul 29.