ALBERT

Description: Abstract 2881 Multiple myeloma (MM) is characterized by a remarkable heterogeneity in outcome following standard and high-dose therapies. Significant efforts have been made to identify genetic changes and signatures that can predict clinical outcome and include them in the routine clinical care. Gene expression profiling (GEP) studies have achieved a central role in the study of multiple myeloma (MM), as they become a critical component in the risk-based stratification of the disease. To molecularly stratify disease-risk groups, we performed GEP on purified plasma cells (obtained from the immunobead selection of CD138+ cells) from 489 MM samples in different stages of the disease using the Affymetrix U133Plus2.0 array. A total of 162 probes were analyzed using an in house automated script to generate a GEP report with the most used risk stratification indices and signatures, including the UAMS 70-gene, UAMS class, TC classification, proliferation and centrosome signature, and NFKB activation indices. In a subset of 57 samples, IgH translocations were analyzed using FISH and results were correlated with GEP data. A macrophage index was calculated and used as a surrogate measurement of non-plasma cell contamination. A total of 49 samples (10%) were excluded from subsequent analysis as the macrophage index indicated a significant contamination with no plasma cells, hence potentially compromising the results. The percent of high-risk disease patients identified from different signatures ranged from 26.4% by using high proliferation index to 28.8% with high centrosome signature and 31.3% with high 70-gene index. This percent of high-risk cases based on the 70-gene index is similar to what was found in Total therapy 2 (TT2) and TT3 cohorts. A third of patients (33.2%) were classified as D1 in the TC class, followed by 11q13 (19.3%), D2 (16.4%), 4p16 (13.8%), MAF (6.1%), None (4.7%), D1+D2 (4.5%) and 6p21 (1.8%). The NF-kB pathway was likely activated in 45.5% to 59.5% of cases, depending on the index used for its calculation. High proliferation index and high centrosome signature significantly correlates with 70-gene high-risk group (p