Gene Expression Profiling (GEP) of Whole Bone Marrow Biopsies in Complete Remission (BMB-CR) of Multiple Myeloma (MM) Patients Treated On Total Therapy Protocols – Normalization of GEP Signature in Comparison with Normal Donor BMB (BMB-NL) and Consequences for Progression-Free Survival (PFS)

Abstract 198 GEP of purified plasma cells (PC) provides superb risk discrimination for PFS and overall survival (OS). It is well established that MM engages the BM micro-environment (ME) and subjugates it toward its survival and progression. International Myeloma Working Group- and flow-based CR have been linked to PFS and OS, but do not provide guidance vis-à-vis the duration of post-transplant consolidation and maintenance therapy. We reasoned that ME may still be altered in flow-CR as it may remain MM-impregnated long after CR is established; conversely, ME normalization may happen much earlier. In a first step, 20 BMB-NL were compared with 331 untreated patients with MM (BMB-MM), leading to the discovery of a 65 gene score (GEP-65), which was then applied to 83 patients with MGUS/asymptomatic multiple myeloma (AMM) and 88 MM patients in CR. GEP-65 risk scores were similar in BMB-CR and BMB-MGUS-AMM contrasting with significantly lower values for BMB-MM. Next we examined PFS for CR patients according to whether BMB-CR signature normalized (BMB-CR-NL, n=14) or failed to normalize (BMB-CR-MM, n=74). A borderline significantly superior PFS was observed in the former group suffering 2 events versus 31 in the remainder (p=0.08). We conclude that (1) BMB-MM differs markedly from BMB-NL, (2) BMB-CR resembles BMB-MGUS-AMM, and (3) BMB-CR-NL can be distinguished from BMB-CR-MM resulting in PFS differences. Availability of several hundred BMB-CR samples and nearly 100 BMB-NL will have been evaluated at the time of the meeting to address the following: (a) can these results be validated, (b) what is the time course of BMB-CR-NL and pattern to BMB-CR-MM and BMB-MM, (c) are there MM GEP molecular subgroup- and risk-dependent differences. Disclosures: Dhodapkar: Celgene: Research Funding; KHK: Research Funding.