KIR2DL5B Associated With Poor Response in CML Treated With Sequential Imatinib, Nilotinib

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KIR2DL5B is associated with poor molecular response and survival in chronic myeloid leukemia treated with imatinib/nilotinib.
KIR2DL5B is associated with poor molecular response and survival in chronic myeloid leukemia treated with imatinib/nilotinib.

KIR2DL5B is associated with poor molecular response and transformation-free survival in patients with chronic myeloid leukemia (CML) treated with sequential imatinib/nilotinib, a new study published online ahead of print in the journal Blood has shown.1

The TIDEL-II study evaluated sequential imatinib/nilotinib in 210 patients with chronic phase CML. The study found that using first-line imatinib to treat CML, with selective nilotinib switching, led to excellent molecular response and survival, and may be preferable to universal first-line use of more potent agents.2

Because killer immunoglobulin-like receptors (KIR) on natural killer cells have been shown to predict response in patients with chronic phase CML treated with tyrosine kinase inhibitors, researchers performed KIR genotyping in 148 newly diagnosed patients enrolled to the TIDEL-II study.

Results showed that the KIR2DL5B gene is associated with inferior transformation-free survival and event-free survival. Researchers also found that the gene is an independent predictor of inferior major molecular response and molecular response.

The findings suggest that natural killer cells play an important early role in facilitating response to imatinib that cannot be overcome with dose intensification or switching to nilotinib.

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“KIR genotyping may add valuable prognostic information to future baseline predictive scoring systems in CP-CML patients and facilitate optimal frontline treatment selection,” the authors concluded.

Reference

  1. Yeung DT, Tang C, Vidovic L, et al. KIR2DL5B genotype predicts outcomes in CML patients treated with response directed sequential imatinib / nilotinib strategy [published online ahead of print October 23, 2015]. Blood. doi: 10.1182/blood-2015-07-655589.
  2. Yeung DT, Osborn MP, White DL, et al. TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets. Blood. 2015; 125(6):915-923.

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