Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicinReportar como inadecuado




Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Annals of Hematology

, Volume 89, Issue 11, pp 1133–1140

First Online: 08 June 2010Received: 06 March 2010Accepted: 11 May 2010

Abstract

Single nucleotide polymorphisms SNPs in the multiple drug resistance protein 1 MRP1 and P-glycoprotein 1 MDR1 genes modulate their ability to mediate drug resistance. We therefore sought to retrospectively evaluate their influence on outcomes in relapsed and-or refractory myeloma patients treated with bortezomib or bortezomib with pegylated liposomal doxorubicin PLD. The MRP1-R723Q polymorphism was found in five subjects among the 279 patient study population, all of whom received PLD + bortezomib. Its presence was associated with a longer time to progression TTP; median 330 vs. 129 days; p = 0.0008, progression-free survival PFS; median 338 vs. 129 days; p = 0.0006, and overall survival p = 0.0045. MDR1-3435C > T, which was in Hardy–Weinberg equilibrium, showed a trend of association with PFS p = 0.0578, response rate p = 0.0782 and TTP p = 0.0923 in PLD + bortezomib patients, though no correlation was found in the bortezomib arm. In a recessive genetic model, MDR1-3435 T was significantly associated with a better TTP p = 0.0405 and PFS p = 0.0186 in PLD + bortezomib patients. These findings suggest a potential role for MRP1 and MDR1 SNPs in modulating the long-term outcome of relapsed and-or refractory myeloma patients treated with PLD + bortezomib. Moreover, they support prospective studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients.

KeywordsBortezomib MDR1 MRP1 Multiple myeloma Pegylated liposomal doxorubicin SNP These data were presented in part at the 51st Annual Meeting and Exposition of the American Society of Hematology in New Orleans, LA, USA, December 6, 2009.

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Autor: Gabriele Buda - Deborah Ricci - C. Chris Huang - Reyna Favis - Nadine Cohen - Sen H. Zhuang - Jean-Luc Harousseau - Piete

Fuente: https://link.springer.com/



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