Minimal Residual Disease (MRD) Assessment before and after Autologous Hematopoietic Cell Transplantation (AutoHCT) and Maintenance for Multiple Myeloma (MM): Results of the Prognostic Immunophenotyping for Myeloma Response (PRIMeR) Study

PRIMeR is the first U.S.-based ancillary study of MRD assessment by multiparameter flow cytometry (MFC). Patients were enrolled on a national 3-arm RCT (BMT CTN 0702, STAMiNA trial, ClinicalTrials.gov Identifier: NCT01109004) comparing 1) tandem auto-HCT, 2) single auto-HCT and 3) single auto-HCT, 4 cycles of lenalidomide, bortezomib, dexamethasone consolidation (auto+RVD); all 3 treatment arms included continuous lenalidomide maintenance until MM progression. STAMiNA opened to accrual before PRIMeR initiated, therefore 437 of 758 patients enrolled in STAMiNA provided consent and at least one analyzable sample for MRD by MFC to PRIMeR. Disease responses and progressions were adjudicated by an independent review committee. All analyses of treatment arm were performed using intent-to-treat. The MFC panel included 10 monoclonal antibodies (CD38, CD138, CD45, CD56, CD19, CD20, CD27, CD28, kappa, lambda) measured via 3 tubes of 6 colors each with a target of analyzing 2.5 × 10 5 -1.5 × 10 6 events, depending on sample quality and quantity, yielding a sensitivity of 10 −5 to 10 −6 . All samples were interpreted by two experienced flow cytometrists who were blinded to treatment arm and other patient, disease and treatment characteristics. MRD was assessed at Baseline/pre-AutoHCT (BL), Pre-maintenance (PM), and 1 year (Y1) post AutoHCT with the primary endpoint of MRD negative at Y1. At a median follow-up of 38 months, there was no significant difference in PFS or OS by treatment arm in the subset of PRIMeR patients. Univariate analysis demonstrated that being MRD negative at PM and Y1 was associated with better PFS, and at Y1, patients who were MRD negative also had longer OS (Table 1, Figures). Multivariate analysis of time to progression or death, adjusting for disease risk, demonstrated hazard ratios (HR) in MRD negative patients compared to MRD positive patients at BL, PM and Y1 were 0.66 (p=0.07), 0.48 (0