denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Program: Oral and Poster Abstracts
Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster I
Methods We first analyzed the miRNAs content of circulating exosomes in MM by small RNA sequencing of 10 samples from MM patients and 5 healthy controls. We then analyzed 156 serum samples from newly diagnosed patients with MM, uniformly treated with a Bortezomib and Dexamethasone based regimen. Using a quantitative RT-PCR array for 23 miRNAs, we assessed the associations between exosomal miRNAs and progression-free survival.
Findings By next generation sequencing, we identified 158 differentially expressed miRNAs in MM compared to normal healthy controls, notably including let-7 family members, miR-17/92 or miR-99b/125a clusters. We further identified a three-miRNA signature based on 156 MM samples (combining miR-106b, miR-18a and let-7e) and calculated a risk score to classify patients as high risk or low risk. Compared to low risk score, patients with a high risk score had a shorter PFS in the training set (hazard ratio [HR] 1·8, 95% CI 1·0-3·0; p=0·0375) and the validation set (HR 2·6, 1·5-4·4; p=0·0005). To further validate this signature, we generated 500 randomly computed re-sampling of the data sets. The three-miRNA signature was consistently significant with a p-value < 0·05 in more than 78% and < 0·10 in 86% of the 500 randomizations. The circulating exosomal miRNA signature was an independent prognostic marker after adjusting for cytogenetics and ISS. In a receiver operating characteristic (ROC) analysis, a combination of this signature together with International Staging System (ISS) and cytogenetics had a better prognostic value than ISS and cytogenetics alone in the training set (2 years area under the ROC curve 0·64 [95% CI 0·56-0·72] vs. 0·60 [95% CI 0·52-0·69]) and the validation set (0·67 [0·59-0·75] vs. 0·58 [0·50-0·66]).
Interpretation This study demonstrates unprecedented evidence of the prognostic significance of exosomal miRNAs in patients with MM. We identified a three-miRNA signature in circulating exosomes that adds prognostic value to ISS and cytogenetic status and helps improve prognostic identification of newly diagnosed MM patients.
Disclosures: Avet-Loiseau: jansen: Membership on an entity’s Board of Directors or advisory committees ; BMS: Membership on an entity’s Board of Directors or advisory committees ; celgene: Membership on an entity’s Board of Directors or advisory committees ; onyx: Membership on an entity’s Board of Directors or advisory committees ; onyx: Membership on an entity’s Board of Directors or advisory committees ; jansen: Membership on an entity’s Board of Directors or advisory committees ; millenium: Membership on an entity’s Board of Directors or advisory committees ; millenium: Membership on an entity’s Board of Directors or advisory committees ; BMS: Membership on an entity’s Board of Directors or advisory committees . Moreau: Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity’s Board of Directors or advisory committees . Facon: Onyx: Membership on an entity’s Board of Directors or advisory committees ; Millenium: Membership on an entity’s Board of Directors or advisory committees ; Janssen: Membership on an entity’s Board of Directors or advisory committees , Speakers Bureau ; BMS: Membership on an entity’s Board of Directors or advisory committees ; Celgene: Membership on an entity’s Board of Directors or advisory committees , Speakers Bureau ; Novartis: Membership on an entity’s Board of Directors or advisory committees ; Amgen: Membership on an entity’s Board of Directors or advisory committees ; Pierre Fabre: Membership on an entity’s Board of Directors or advisory committees .
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