Drug Information

Drug (ID: DG01401) and It's Reported Resistant Information

• Name: Mogamulizumab
• Indication:
  In total 7 Indication(s)
  Cutaneous T-cell lymphoma [ICD-11: 2B00]; Approved; [1]
  Mycosis fungoides [ICD-11: 2B01]; Approved; [1]
  Mycosis fungoides [ICD-11: 2B01]; Approved; [1]
  Sezary syndrome [ICD-11: 2B02]; Approved; [1]
  Sezary syndrome [ICD-11: 2B02]; Approved; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Approved; [1]
  T-cell leukaemia [ICD-11: 2A90]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Cutaneous T-cell lymphoma [ICD-11: 2B00]; [1]
• Target: C-C chemokine receptor type 4 (CCR4); CCR4_HUMAN; [1]
• TTD Drug ID: D0W2HD

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Cutaneous T-cell lymphoma [ICD-11: 2B00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: C-C motif chemokine receptor 4 (CCR4) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Cutaneous T-cell lymphomas [ICD-11: 2B00.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Immunohistochemistry assay
• Mechanism Description: We identified 17 patients with mycosis fungoides or Sezary syndrome who either were intrinsically resistant or acquired resistance to mogamulizumab. Low expression of CCR4 by immunohistochemistry or flow cytometry was found in 65% of patients. Novel emergent CCR4 mutations targeting the N-terminal and transmembrane domains were found in 3 patients after disease progression. Emerging CCR4 copy number loss was detected in 2 patients with CCR4 mutations. Acquisition of CCR4 genomic alterations corresponded with loss of CCR4 antigen expression. We also report on outcomes of three cutaneous T-cell lymphoma patients with gain-of-function CCR4 mutations treated with mogamulizumab. Our study indicates that resistance to mogamulizumab in CTCL frequently involves loss of CCR4 expression and emergence of CCR4 genomic alterations.

References

• Ref 1: Resistance to mogamulizumab is associated with loss of CCR4 in Cutaneous T-cell Lymphoma .Blood. 2022 Apr 18:blood.2021014468. doi: 10.1182/blood.2021014468. Online ahead of print. 10.1182/blood.2021014468