Assessment of Treatment Response By Ife, Next Generation Flow Cytometry and Mass Spectrometry Coupled with Liquid Chromatography in the GEM2012MENOS65 Clinical Trial

Introduction: In patients (pts) with multiple myeloma (MM), next generation flow cytometry (NGF) and next generation sequencing have shown an increased capacity to identify the presence of disease and to anticipate patient's prognosis as compared to serum protein immunofixation (IFE). However, both methods rely on bone marrow (BM) samples and it is important to explore alternative techniques applicable in more accessible samples such as peripheral blood. Patients and Methods: Newly diagnosed MM pts enrolled in the PETHEMA/GEM2012MENOS65 trial received six cycles of induction with bortezomib, lenalidomide and dexamethasone (VRD), intensification with high-dose therapy (melphalan or busulfan and melphalan) followed by autologous stem cell transplantation and consolidation with two more cycles of VRD. At the end of the treatment (post-consolidation), the M-protein (MP) was analyzed in serum by conventional IFE and by EXENT Quantitative Immunoprecipitation Mass Spectrometry using IgG/A/M, κ, λ, free κ and free λ isotypic beads; negative samples by EXENT were re-analyzed by liquid chromatography mass spectrometry (LC-MS). The presence of clonal plasma cells in BM samples was investigated by NGF following the Euroflow guidelines (sensitivity≥10 -5). Samples from the first 164 pts enrolled in the trial were analyzed in this study. Results: After consolidation, persistent disease was detected in 42 (26%) pts by IFE, in 56 (34%) by EXENT and in 72 (44%) by NGF. Surprisingly, the presence or absence of disease by IFE did not discriminate pts with different progression-free survival (PFS), but both EXENT and NGF segregated two cohorts with a significantly different PFS (p=0.0016 and p