The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD)

Abstract

The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is to obtain an early and deep tumour burden reduction, up to the level of complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC obtained at baseline from MM patients in CR after bortezomibthalidomide-dexamethasone (VTD) first line therapy.One hundred and eighteen MM primary tumours obtained from homogeneously treated patients were profiled both for gene expression and for single nucleotide polymorphism genotype. Genomic results were used to obtain a predictor of sensitivity to VTD induction therapy, as well as to describe both the transcription and the genomic profile of PC derived from MM with subsequent optimal response to primary induction therapy.By analysing the gene profiles of CR patients, we identified a 5-gene signature predicting CR with an overall median accuracy of 75% (range: 72%-85%). In addition, we highlighted the differential expression of a series of genes, whose deregulation might explain patients' sensitivity to VTD therapy. We also showed that a small copy number loss, covering 606Kb on chromosome 1p22

IKAROS expression in distinct bone marrow cell populations as a candidate biomarker for outcome with lenalidomide‐dexamethasone therapy in multiple myeloma

“…In MM cells, GEP determined IKZF1 mRNA expression was linked to response and outcome in pomalidomide treated patients . Interestingly, IKZF1 expression levels were also reported to be associated with complete response in patients treated with bortezomib, thalidomide and dexamethasone . In contrast, we did not find an association between baseline IKAROS protein levels in MM cells and OS.…”

Whole exome precision oncology targeting synthetic lethal vulnerabilities across the tumor transcriptome

“…Cancer types are noted on the top of each dataset. (B) ROC curves for breast cancer patients treated with lapatinib (GSE66399) 22 , gefinitib (GSE33658) 23 , letrozole (GSE16391) 24 , doxorubicin (GSE8465) 25 , trastuzumab (GSE76360) 26 , everolimus (GSE119262) 27 and cetuximab (GSE23428) 28 , ovarian cancer patients treated with dasatinib (GSE37180) 29 , non-small cell lung cancer patients treated with sorafenib (GSE33072) 32 , colorectal cancer patients treated with irinotecan (GSE72970) 30 , multiple myeloma patients treated with bortezomib (GSE68871) 31 . (C) Bar graphs show the predictive accuracy in terms of AUCs (Y-axis) of SL-based predictors and a variety of controls specified earlier in Figure 1E (X-axis).…”

Standardisation of minimal residual disease in multiple myeloma

“…The gene expression profile (GEP) evaluation is the subject of many studies with the aim of better defining the prognostic risk of MM at the onset, but very little as a tool for evaluation of response (Terragna et al, 2016). U266-LR7 and RPMI-8266).…”

“…The gene expression profile (GEP) evaluation is the subject of many studies with the aim of better defining the prognostic risk of MM at the onset, but very little as a tool for evaluation of response (Terragna et al, 2016). The data collected in literature about evaluation of GEP in MRD clonal PCs are limited, principally due to the characteristics of the sample and the amount of cells that allow appropriate RNA extraction.…”