Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-11

AUTHORS

Gabriele Buda, Deborah Ricci, C. Chris Huang, Reyna Favis, Nadine Cohen, Sen H. Zhuang, Jean-Luc Harousseau, Pieter Sonneveld, Joan Bladé, Robert Z. Orlowski

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). MDR1/3435(C > 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. More... »

PAGES

1133-1140

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00277-010-0992-3

DOI

http://dx.doi.org/10.1007/s00277-010-0992-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051097530

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20532504


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