Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/20717
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dc.contributor.authorMithraprabhu, Sridurga-
dc.contributor.authorMorley, Rachel-
dc.contributor.authorKhong, Tiffany-
dc.contributor.authorKalff, Anna-
dc.contributor.authorBergin, Krystal-
dc.contributor.authorHocking, Jay-
dc.contributor.authorSavvidou, Ioanna-
dc.contributor.authorBowen, Kathryn M-
dc.contributor.authorRamachandran, Malarmathy-
dc.contributor.authorChoi, Kawa-
dc.contributor.authorWong, Boris Ka Leong-
dc.contributor.authorReynolds, John-
dc.contributor.authorSpencer, Andrew-
dc.date2019-04-16-
dc.date.accessioned2019-04-30T23:55:27Z-
dc.date.available2019-04-30T23:55:27Z-
dc.date.issued2019-04-16-
dc.identifier.citationLeukemia 2019; online first: 16 April-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/20717-
dc.description.abstractMonitoring tumour burden and therapeutic response through analyses of circulating cell-free tumour DNA (ctDNA) and extracellular RNA (exRNA) in multiple myeloma (MM) patients were performed in a Phase Ib trial of 24 relapsed/refractory patients receiving oral azacitidine in combination with lenalidomide and dexamethasone. Mutational characterisation of paired BM and PL samples at study entry identified that patients with a higher number of mutations or a higher mutational fractional abundance in PL had significantly shorter overall survival (OS) (p = 0.005 and p = 0.018, respectively). A decrease in ctDNA levels at day 5 of cycle 1 of treatment (C1D5) correlated with superior progression-free survival (PFS) (p = 0.017). Evaluation of exRNA transcripts of candidate biomarkers indicated that high CRBN levels coupled with low levels of SPARC at baseline were associated with shorter OS (p = 0.000003). IKZF1 fold-change <0.05 at C1D5 was associated with shorter PFS (p = 0.0051) and OS (p = 0.0001). Furthermore, patients with high baseline CRBN coupled with low fold-change at C1D5 were at the highest risk of progression (p = 0.0001). In conclusion, this exploratory analysis has provided the first demonstration in MM of ctDNA for predicting disease outcome and of the utility of exRNA as a biomarker of therapeutic response.-
dc.language.isoeng-
dc.titleMonitoring tumour burden and therapeutic response through analysis of circulating tumour DNA and extracellular RNA in multiple myeloma patients.-
dc.typeJournal Article-
dc.identifier.journaltitleLeukemia-
dc.identifier.affiliationFaculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australiaen
dc.identifier.affiliationDepartment of Clinical Hematology, Monash University, Clayton, Victoria, Australiaen
dc.identifier.affiliationEpidemiology and Preventive Medicine, Alfred Health-Monash University, Clayton, Victoria, Australiaen
dc.identifier.affiliationTranslational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationMyeloma Research Group, Australian Centre for Blood Diseases, Alfred Hospital-Monash University, Melbourne, Victoria, Australiaen
dc.identifier.affiliationMalignant Hematology and Stem Cell Transplantation, Alfred Hospital, Melbourne, Victoria, Australiaen
dc.identifier.affiliationHaematology, Box Hill Hospital, Melbourne, Victoria, Australiaen
dc.identifier.doi10.1038/s41375-019-0469-x-
dc.identifier.orcid0000-0002-8825-8625-
dc.identifier.pubmedid30992504-
dc.type.austinJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
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