Presence of KIR2DL5B Gene Predicts Poor Response in Newly Diagnosed Chronic Leukemia

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Presence of KIR genotype 2DL5B independently associated with poor response in CML.
Presence of KIR genotype 2DL5B independently associated with poor response in CML.

SAN FRANCISCO—Presence of the killer immunoglobulin-like receptor (KIR) genotype 2DL5B was independently associated with poor response in patients with de novo chronic myelocytic leukemia in chronic phase (CML-CP) treated with imatinib and switched to nilotinib, the TIDEL-II study (Abstract 814) concluded at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.

This included inferior major molecular response (MMR), MR4.5, progression-free survival (PFS), which was 90.3% at 2 years compared with 97.2% in patients who were KIR2DL5B negative (P=0.04), and failure-free survival (FFS), which was 66.8% versus 85.5%, respectively , said David T. Yeung, MBBS,  of the Department of Genetics and Molecular Pathology, Centre for Cancer Biology in Adelaide, Australia.

The KIR genes are located in the centromeric and telomeric regions of chromosome 19 and are highly individualized alleles, Yeung explained.

The prospective study started 210 patients on imatinib 600 mg once daily. Patients were monitored for BCF-ABL 10% at 3 months, 1% at 6 months, and 0.1% at 12 months. In cohort 1 (105 patients), patients who failed these targets were dose escalated to imatinib 800 mg.

If they subsequently failed to achieve these targets or were already on the higher imatinib dose, they were switched to nilotinib 400 mg twice daily. In cohort 2 (105 patients), patients who failed these targets were switched to nilotinib regardless of imatinib dose.

Baseline samples available for 148 patients were retrospectively genotyped for KIR. Molecular response and survival outcomes were analyzed as stratified by early molecular response (EMR, BCR-ABL ≤10% at 3 months), gender, Sokal index, age, and KIR genotype.

Study results showed “the KIR2DL5B allele correlated with lower rates of MMR and MR4.5 in a multivariate analysis, even in a treatment schema allowing patients failing early molecular targets to be treated with nilotinib, independent of EMR,” Dr. Yeung said. “Additionally, KIR2DL5B positivity was associated with inferior PFS and FFS.”

He said these data confirm that prognostic significance of EMR, with KIR genotyping further refining the prognosis of patients failing to achieve EMR. “Prognostic markers available at CML-CP diagnosis, such as KIR genotypes, may have clinical utility,” he said.

“Furthermore, the KIR genotype may provide useful information in combination with other biomarkers and could be incorporated into future prognostic scoring systems for CML-CP.”

Reference

  1. Yeung, David T., BSc, MBBS, FRACP, FRCPA, et al. "814 KIR2DL5B Genotype Independently Predicts Poor Outcomes in CML-CP Patients Switched to Nilotinib after Suboptimal Responses to Imatinib and May Refine Prognosis in Patients with EMR Failure." ASH 2014. Oral Presentation. December 9, 2014.

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