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Pharmacokinetics and pharmacodynamics
PKP-005 Prognostic impact of novel gene polymorphisms in newly diagnosed acute myeloid leukaemia adults undergoing induction chemotherapy
  1. J Megías Vericat1,
  2. P Montesinos2,
  3. M Herrero3,
  4. F Moscardó2,
  5. V Bosó1,
  6. D Martínez-Cuadrón2,
  7. L Rojas4,
  8. S Aliño5,
  9. M Sanz2,
  10. J Poveda6
  1. 1Hospital Universitario Y Politécnico La Fe, Servicio de Farmacia Área Del Medicamento, Unidad de Farmacogenética, Instituto Investigación Sanitaria La Fe, Valencia, Spain
  2. 2Hospital Universitario Y Politécnico La Fe, Servicio de Hematología Y Hemoterapia, Valencia, Spain
  3. 3Hospital Universitario Y Politécnico La Fe and Facultad de Medicina, Universidad de Valencia, Unidad de Farmacogenética Instituto Investigación Sanitaria La Fe and Área Del M, Valencia, Spain
  4. 4Hospital Universitario Y Politécnico La Fe and Pontificia Universidad Católica de Chile, Unidad de Farmacogenética Instituto Investigación Sanitaria La Fe and Área Del Medicamento, and Department of Internal Medicine, Faculty of Medicine, Valencia, Spain
  5. 5Hospital Universitario Y Politécnico La Fe and Universidad de Valencia, Unidad de Farmacogenética and Unidad de Farmacología Clínica-Área Del Medicamento, Instituto Investigación Sanitaria La Fe and Área Del Medicamento, and Departamento Farmacología, Valencia, Spain
  6. 6Hospital Universitario Y Politécnico La Fe, Servicio de Farmacia Área Del Medicamento, Valencia, Spain

Abstract

Background Single nucleotide polymorphisms (SNPs) could lead to inter-individual differences in treatment outcomes.

Purpose A recent study1 reported several novel SNPs involved in cytarabine cytotoxicity using a whole-genome approach, which were associated with clinical outcomes in a paediatric AML population. However their association with effectiveness and toxicity remain undetermined in adults.

Material and methods The six SNPs with clinical significance in the Gamazon study1 (Table 1) were evaluated in 109 adult patients at initial diagnosis with AML using a mass spectrometry–based multiplex genotyping assay (Sequenom). All patients were treated with idarubicin plus cytarabine.

Genotypes were grouped as dichotomous variables (dominant/recessive model). Efficacy was evaluated comparing complete remission (CR) vs. partial remission or resistance. Toxicities were grouped as binary variables (grade: 0–1 vs. grade: 2–4, Who scale). Haematological toxicity was measured with the time to neutropenia/thrombocytopenia recovery since first day of chemotherapy. Variables were assessed using χ2 and Mann–Whitney U tests.

Results The median age of patients was 53 years (17–78 years). Among the baseline characteristics analysed (age, gender, haemoglobin, leukocyte, platelet and peripheral or BM blasts count) there was significant difference in genotype distributions regarding age (wild allele carriers of rs9883101 were older, p = 0.02) and gender (men had a higher proportion of variant alleles for rs6550826 and rs7729269, p = 0.003 and 0.006; and wild allele for rs2897047, p = 0.005). Toxicities were more frequent with variant alleles of several SNPs (table), but they were not associated with the CR rates.

Conclusion We obtained new associations of these novel polymorphisms with toxicity, not previously studied in adult AML patients, but not in effectiveness. These SNPs could be useful biomarkers in clinical practice.

View this table:
Abstract PKP-005 Table 1

Reference

  1. Gamazon ER, Lamba JK, Pounds S, et al. Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model identifies polymorphisms associated with outcome in AML patients. Blood 2013;121(21):4366–76

ReferenceNo conflict of interest.

https://doi.org/10.1136/ejhpharm-2015-000639.321

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