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  • Jakobsen Falk, IngridLinköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten (author)

Pharmacogenetic study of the impact of ABCB1 single-nucleotide polymorphisms on lenalidomide treatment outcomes in patients with multiple myeloma: results from a phase IV observational study and subsequent phase II clinical trial

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2017-11-25
  • SPRINGER,2018
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-144446
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-144446URI
  • https://doi.org/10.1007/s00280-017-3481-8DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:137391334URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|Swedish Cancer Society; Swedish Research Council; AFA Insurance; Linkoping University; ALF Grants, Region Ostergotland; Celgene Corporation
  • Purpose Despite therapeutic advances, patients with multiple myeloma (MM) continue to experience disease relapse and treatment resistance. The gene ABCB1 encodes the drug transporter P-glycoprotein, which confers resistance through drug extrusion across the cell membrane. Lenalidomide (Len) is excreted mainly via the kidneys, and, given the expression of P-gp in the renal tubuli, single-nucleotide polymorphisms (SNPs) in the ABCB1 gene may influence Len plasma concentrations and, subsequently, the outcome of treatment. We, therefore, investigated the influence of ABCB1 genetic variants on Len treatment outcomes and adverse events (AEs). Methods Ninety patients with relapsed or refractory MM, who received the second-line Len plus dexamethasone in the Rev II trial, were genotyped for the ABCB1 SNPs 1199G amp;gt; A (Ser400Asn, rs2229109), 1236C amp;gt; T (silent, rs1128503), 2677G amp;gt; T/A (Ala893Ser, rs2032582), and 3435C amp;gt; T (silent, rs1045642) using pyrosequencing, and correlations to response parameters, outcomes, and AEs were investigated. Results No significant associations were found between genotype and either best response rates or hematological AEs, and 1236C amp;gt; T, 2677G amp;gt; T or 3435C amp;gt; T genotypes had no impact on survival. There was a trend towards increased time to progression (TTP) in patients carrying the 1199A variant, and a significant difference in TTP between genotypes in patients with standard-risk cytogenetics. Conclusions Our findings show a limited influence of ABCB1 genotype on lenalidomide treatment efficacy and safety. The results suggest that 1199G amp;gt; A may be a marker of TTP following Len treatment in standard-risk patients; however, larger studies are needed to validate and clarify the relationship.

Subject headings and genre

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  • Lund, JohanKarolinska Institutet,Karolinska Institute, Sweden (author)
  • Green, HenrikLinköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden(Swepub:liu)hengr89 (author)
  • Gruber, AstridKarolinska Institute, Sweden (author)
  • Alici, EvrenKarolinska Institutet,Karolinska Institute, Sweden (author)
  • Lauri, BirgittaSunderby Hospital, Sweden (author)
  • Blimark, CecilieSahlgrens University Hospital, Sweden (author)
  • Mellqvist, Ulf-HenrikSouth Elvsborg Hospital, Sweden (author)
  • Swedin, AgnetaSkåne University Hospital, Sweden (author)
  • Forsberg, KarinNorrland University Hospital, Sweden (author)
  • Carlsson, ConnyHallands Hospital, Sweden (author)
  • Hardling, MatsUddevalla Central Hospital, Sweden (author)
  • Ahlberg, LuciaRegion Östergötland, Hematologiska kliniken US(Swepub:liu)lucah64 (author)
  • Lotfi, KouroshLinköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US(Swepub:liu)koulo97 (author)
  • Nahi, HarethKarolinska Institutet,Karolinska Institute, Sweden (author)
  • Linköpings universitetAvdelningen för läkemedelsforskning (creator_code:org_t)

Related titles

  • In:Cancer Chemotherapy and Pharmacology: SPRINGER81:1, s. 183-1930344-57041432-0843

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