Minimal Residual Disease and Biomarkers ASH 2015 Summary 57th ASH Annual Meeting and Exposition. Orlando, FL Mutational Profile And Prognostic Relevance of Circulating Tumor Cells in Multiple Myeloma Y Mishima *, B Paiva *, J Shi *, M Massoud, S Manier, L Flores, A Perilla- Glen, Y Aljawai, S Takagi, D Huynh, AM Roccaro, A Sacco, D Alginani, MV Mateos, J Blade, JJ Lahuerta, P Richardson, J Laubach, R Schlossman, K Anderson, N Munshi, F Prosper, JF San Miguel *, F Michor *, IM Ghobrial * 57th ASH Annual Meeting and Exposition. Orlando, FL Time from CTC detection (months) Time-to progression (%) CTC 0.001% (n=40) No CTC (n=10) Newly diagnosed transplant-ineligible Prognostic relevance of CTC detection in newly-diagnosed and relapsed MM Mishima Y, et al. Blood : Time from CTC detection (months) sequential PB samples at relapse (median of 3 per patient) Number of SNVs detected CTCs show less SNVs as compared to patient-paired BM clonal PCs Percentages of shared SNVs 79% of CTC-SNVs were identified in patient-paired BM clonal PCs Mishima Y, et al. Blood :23 Concordance of SNVs in driver genes BM CTC BM CTC Log2 Ratio Concordance of CNVs between matched CTCs and BM clonal PCs without WGA Mishima Y, et al. Blood :23 Conclusions This study provides the rational for an integrated flow- molecular algorithm to detect CTCs in PB, and to identify candidate patients for noninvasive genomic characterization Mutational profile of CTCs mirrors a significant fraction (~80%) of the genomic variants present in BM clonal PCs, but may miss up to one-third (35%) of mutations specifically detected in BM clonal PCs CTCs could potentially be used as a noninvasive biomarker to monitor MM drivers (e.g.: KNRAS, NRAS, BRAF, IRF4) Mishima Y, et al. Blood :23 Evaluation of circulating tumour DNA (ctDNA) for the mutational characterisation of multiple myeloma Andrew Spencer 1, Sridurga Mithraprabhu 1, Malarmathy Ramachandran 1, Daniela Klarica 1, Jay Hocking 1, Laura Mai 2, Stephanie Walsh 2, David Broemeling 2, Andre Marziali 2, Anna Kalff 1, Matthew Wiggin 2, Brian Durie 3, Tiffany Khong 1 1 Alfred Health-Monash University, Melbourne, Australia; 2 Boreal Genomics, Vancouver, Canada; 3 Samuel Oschin Comprehensive Cancer Institute, Los Angeles, USA Paired BM & plasma samples from 10 NDMM & 18 RRMM patients cfDNA CD138+ PC Cellular DNA OMD 42 mutations ddPCR 3 WT DNA controls Spencer A, et al. Blood :368 85 KRAS, NRAS, TP53, BRAF mutations detected in 23 MM patients 0 mutations in 5 MM patients and 3WT controls 31 of 42 represented OMD mutations detected Spencer A, et al. Blood :368 ctDNA ddPCR: Patient #14. Non-secretory MM. Marrow PC 20% 90%100%20%5% MONTHS Fractional Abundance VCD ASCT VCD T-DCEP ***** Spencer A, et al. Blood :368 CONCLUSIONS These data provide proof of concept that evaluable plasma- derived ctDNA is present in MM and that it can be interrogated to provide additional mutational data on patients. The sub-clonal architecture in some patients may be more complex than suggested by prior NGS studies with a greater prevalence of RAS mutations than previously described. Sequential ctDNA analysis may represent a non-invasive approach for therapeutic monitoring and to inform treatment decisions. Spencer A, et al. Blood :368 What Is the Frequency of Transplant-Eligible Multiple Myeloma Patients Being Cured? The Impact of an MGUS-like Signature at Diagnosis and MRD-Negativity B Paiva, MB Vdriales, N Puig, MT Cedena, L Cordon, MV Mateos, J Martnez- Lpez, L Rosiol, A Garca de Coca, N de las Heras, J Galende, J Hernndez, L Palomera, J De la Rubia, J Blad, JF San Miguel, and JJ Lahuerta, on behalf of the Spanish Myeloma Group (GEM/PETHEMA) 57th ASH Annual Meeting and Exposition. Orlando, FL Diagnosis (n=1075) PETHEMA/GEM2000 protocol Induction 6 alternating cycles of VBMCP/VBAD HDT/ASCT Maintenance Interferon/prednisone for 2y Patients follow-up was updated for the present analysis, and the median follow-up of the series is now of 12-years All patients remaining progression-free and alive but for which the follow-up was inferior to 10-years were excluded from the analysis From a total of 1071 patients, 1030 were eligible for this analysis because they either relapsed or died during the first 10-years from diagnosis, or remained progression-free and alive for more than 10-years 91 patients (9%) remained progression-free and alive for more than 10- years Paiva B, et al. Blood :725 Independent predictive markers for long-term disease control (PFS 10-years) PFS 10y (PFS 3 focal lesions in both univariate and multivariate models. Results McDonald JE, et al. Blood :724 41 TLG assessment is superior to counting the number of focal lesions. It is the optimum method for evaluating the extent of focal lesions and to predict clinical outcome. As this measurement can be standardized using FDA approved software, it should be utilized clinically and in trials going forward. Conclusions McDonald JE, et al. Blood :724