International ImmunopharmacologyVolume 41, 1 December 2016, Pages 42-46

Blinatumomab provoked fatal heart failure(Review)

  • aRecombinant Proteins Department, Breast Cancer Research Center, ACECR, Tehran, Iran
  • bCancer Genetics Department, Breast Cancer Research Center, ACECR, Tehran, Iran
  • cTasnim Biotechnology Research Center (TBRC), School of Medicine, AJA University of Medical Sciences, Tehran, Iran

Abstract

Mentioned in Blinatumomab (Blincyto®) clinical safety report, a 5 year old boy with acute lymphoblastic leukemia (ALL) receiving Blincyto® with the concentration of 30 μg/m2/day on the fourth day of therapy developed both Cytokine Release Syndrome (CRS) and Tumor Lysis Syndrome (TLS). Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Bilirubin peaks were 18, 7 and 8 folds more than upper normal limit (UNL) respectively. However, albumin was reduced to approximately half of the lower Normal limit (LNL). Although Blincyto® administration was immediately withdrawn, he expired in the day 10 due to a fatal cardiac failure. Based on evidence, FDA concluded that CRS was the main cause of death in this patient. Evoking evidence now propose that aberrant pro-inflammatory cytokines secretion, the hallmark of CRS, and subsequent elevation in nitric oxide (NO) can result in both inotropic and chronotropic alterations in myocardial excitation-contraction coupling, myocardial contractility suppression, desensitization of β-adrenergic receptors stimulation, development of acute cardiac failure and death. The probably neglecting point here is that TLS itself can also develop life threatening conditions including sudden cardiac failure through induction of hypocalcemia, hyperkalemia and hyperuricemia, making CRS monitoring and proper required supportive interventions more complex. Here, first we enumerate probable mechanisms through which CRS results in development of fatal cardiac failure and then explain the possible neglected role of TLS in development of the fatal cardiac failure. © 2016

Author keywords

  • Blinatumomab
  • Cardiac contractility suppression
  • Cytokine release syndrome
  • Fatal cardiac failure
  • Tumor lysis syndrome

Indexed keywords

EMTREE drug terms:blinatumomabcytokinenitric oxideantineoplastic agentbispecific antibodyblinatumomab
EMTREE medical terms:clinical featurecytokine release syndromedisease associationdrug mechanismfatalityheart failurehumanhyperkalemiahypocalcemiapriority journalprotein inductionReviewtumor lysis syndromeanimalchemically inducedheart failure
MeSH:AnimalsAntibodies, BispecificAntineoplastic AgentsHeart FailureHumans

Chemicals and CAS Registry Numbers:

blinatumomab, 853426-35-4; nitric oxide, 10102-43-9;

Antibodies, Bispecific; Antineoplastic Agents; blinatumomab

Drug tradename:

  • blincyto
  • ISSN: 15675769
  • CODEN: IINMB
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.intimp.2016.10.017
  • PubMed ID: 27816725
  • Document Type: Review
  • Publisher: Elsevier B.V.

  Majidzadeh-A, K.; Cancer Genetics Department, Breast Cancer Research Center, ACECR, Tehran, Iran; email:[email protected]
© Copyright 2017 Elsevier B.V., All rights reserved.

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