Pharmacogenetic Study on Multiple Myeloma Patients Treated with DAV Regimen and Autologous Stem Cell Transplantation.

As previously reported, genetic variability in xenobiotic metabolism (GSTP1 and NQO1), multidrug resistance (MDR1), folate transport (SLC19A1) and DNA synthesis (TYMS) can influence the outcome after chemotherapy and autologous transplantation in patients with multiple myeloma (MM) (Maggini et., Leuk Res 2007 in press; Buda et al., Leuk Res 2007, 31(8):1029–30; Buda et al., BJH 2007, 137(5):454–6; Maggini et al., Leukemia 2007, 21(1):176–8). To test the reciprocal influence of the examined polymorphisms on the outcome, multivariate analyses were performed on 98 patients receiving DAV regimen, followed by conditioning regimen with melphalan and autologous stem cell transplantation (ASCT) in 84 cases. As shown in table I, a worse outcome following DAV therapy was significantly associated with GSTP1 G/G, SLC19A1 T/T and TYMS A/A genotypes. Only a borderline effect was seen for NQO1 T/T carriers. After ASCT, no significant influence of the analysed polymorphisms was observed, but a higher percentage of responders presented the SLC19A1 T/T genotype. A significantly improved overall survival (OS) was found in patients carrying SLC19A1 T/T genotype or MDR1 T allele (Cox regression analysis, p=0.01). Multivariate analyses confirmed the previously reported findings: the estimated effects are comparable, even though the significance resulted slightly reduced as expected for multiple comparisons. These preliminary results, if sustained by extended analyses, suggest that these polymorphisms could be regarded as pharmacogenetic markers and as prognostic factor in order to predict the outcome of MM patients.

Table I

Multiple genotype testing of MM patients are responders (R) versus non-reponders (NR) to DAV therapy (CT) or ASCT by unconditional logistic regression analysis.

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