Drug Information

Drug (ID: DG00542) and It's Reported Resistant Information

• Name: Inotuzumab ozogamicin
• Synonyms: Inotuzumab ozogamicin
• Indication:
  In total 1 Indication(s)
  Acute lymphoblastic leukaemia [ICD-11: 2A70]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Acute lymphocytic leukemia [ICD-11: 2B33]; [2]
• Target: Inotuzumab ozogamicin; CD22_HUMAN; [1]
• DrugBank ID: DB05889

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: B-cell receptor CD22 (CD22) [2]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Relapsed B-acute Lymphoblastic leukaemia [ICD-11: 2B33.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay (ELISA)
• Mechanism Description: One important escape mechanism at relapse may be modulation of the CD22 antigen expression on leukemic blasts, analogous to antigen loss associated with CD19-directed therapies such as blinatumomab and CD19-CAR T-cell therapies.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: B-cell receptor CD22 (CD22) [1]

• Molecule Alteration: Missense mutation; p.V238 frameshift
• Resistant Disease: Relapsed B-acute Lymphoblastic leukaemia [ICD-11: 2B33.3]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Experiment for Molecule Alteration: Whole genome sequencing assay; Whole transcriptome RNA-sequencing assay
• Experiment for Drug Resistance: Bone marrow biopsy assay; Flow cytometry assay
• Mechanism Description: Decreased surface CD22 expression and receptor density have been reported as mechanisms of acquired@resistance to InO and CD22 CAR-T in some patients relapsing with B-lineage acute leukaemia. Truncating CD22 mutation with concomitant loss of the receptor from the cell surface represents a new mechanism of leukaemic cell escape

References

• Ref 1: Inotuzumab ozogamicin resistance associated with a novel CD22 truncating mutation in a case of B-acute lymphoblastic leukaemiaBr J Haematol. 2020 Oct;191(1):123-126. doi: 10.1111/bjh.16949. Epub 2020 Jul 9.
• Ref 2: LincHOTAIR epigenetically silences miR34a by binding to PRC2 to promote the epithelial-to-mesenchymal transition in human gastric cancer Cell Death Dis. 2015 Jul 2;6(7):e1802. doi: 10.1038/cddis.2015.150.