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Background  The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment.    Methods  Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles  CYP2C19*2  and  CYP2D6*3 ,  *4 ,  *5  (gene deletion),  *6 , and  CYP2D6  gene duplication.    Results  In patients who were treated with bortezomib and were carriers of one or two defective  CYP2D6  alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional  CYP2C19  and  CYP2D6  alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional  CYP2C19  and  CYP2D6  alleles associated with neurological adverse reactions to thalidomide and bortezomib.    Conclusion  There was no association between functional  CYP2C19  and  CYP2D6  alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of  CYP2D6  alleles in treatment outcome.

bmc cancer

No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma