Multiple myeloma (MM) risk is classified using fluorescence in situ hybridization (FISH) routine cytogenetics, and gene expression profiling (GEP). GEP is a clinically validated tool for prognostication of MM in newly diagnosed and relapsed patients (pts), its role in very heavily treated stages is less clear. A study (Nishihori et al, ASH, 2016) concluded that GEP is useful regardless of disease stage. We aim to determine the prognostic significance of GEP heavily pre-treated MM cohort.
299 pts with MyPRSTM GEP results at Hackensack University Medical Center (NJ) between 2012 and 2016 were included. High risk GEP was defined with the validated cutoff score of >45.2, high risk FISH was determined according to the mSMART classification as del17p, t(14,16), t(14,20). Chi-square tests were performed on categorical data and Wilcoxon rank sum tests on continuous data. Overall survival (OS) and progression free survival (PFS) were performed using Kaplan-Meier.
Median age was 63 years (range, 25-91), 170 pts (56%) were men, 81 pts (28%) had International Staging System (ISS) 3 and 191 pts (62%) had Durie-Salmon Staging (DSS) III. 245 pts (81%) had at least one bone marrow transplant (BMT). Median time from myeloma diagnosis to GEP was 30.1 (range 0.1-178.4) months. Most pts had GEP on diagnosis but 24% were heavily pretreated (range, 1-6 lines of treatment), and 13% had a BMT prior to GEP testing. 77 pts (25%) had high-risk disease based on GEP with a median score of 36.5 (range, 9.03-84.05). Molecular subtypes were hyperdiploidy (HY) 31%, cyclin family (CD)-2 20%, low bone disease (LB) 13%, proliferation (PR) 11%, MAF associated (MF) 10%, CD-1 8%, and MMSET associated (MS) 6%. Median OS and PFS were significantly inferior in patients with high-risk by GEP, 25 vs 33 months (p<0.021), 13 vs 21 months (p<0.004) respectively. Molecular subtypes were not individual predictors of OS (p<0.2). When MF, MS and PR subtypes were combined, they had inferior OS compared to other subtypes but this was not statistically significant (p<0.3).
GEP can accurately predict risk status in heavily pre-treated and post-transplant MM pts. In conclusion, our data confirm that GEP is a good prognostic indicator in MM pts irrespective of disease stage and prior treatments. Further prospective studies with larger samples and correlating with baseline and intra-treatment GEP are needed.
Richter: Janssen: Speakers Bureau; BMS: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vesole: Takeda: Speakers Bureau; Celgene: Speakers Bureau. Siegel: Celgene, Takeda, Amgen Inc, Novartis and BMS: Consultancy, Speakers Bureau; Merck: Consultancy. Biran: Takeda: Speakers Bureau; Celgene, Amgen: Consultancy, Speakers Bureau.
Asterisk with author names denotes non-ASH members.