Minimal Residual Disease Status in Multiple Myeloma 1 Year After Autologous Hematopoietic Cell Transplantation and Lenalidomide Maintenance Are Associated With Long-Term Overall Survival.

Abstract

Prognostic Immunophenotyping in Myeloma Response (PRIMeR) is an ancillary study of minimal residual disease (MRD) assessment for multiple myeloma by next-generation multiparameter flow cytometry (MFC). Patients were enrolled on a three-arm randomized control trial (Blood and Marrow Transplants Clinical Trials Network 0702 Stem Cell Transplant for Myeloma in Combination of Novel Agents [STaMINA]; ClinicalTrials.gov identifier: NCT01109004). Four hundred and thirty-five patients consented to the MRD panel, which included 10 monoclonal antibodies measured via six-color MFC. MRD was measured at baseline/preautologous hematopoietic cell transplant (BL/preAutoHCT), premaintenance (PM), and 1 year (Y1) after AutoHCT with a sensitivity of 10^-5 to 10^-6. The primary objective was to assess MRD-negative (MRD^neg) at 1 year after AutoHCT and progression-free survival and overall survival (PFS/OS). Similar to the STaMINA results, at a median follow-up of 70 months, there was no significant difference in PFS/OS by treatment arm in the PRIMeR patients. MRD^neg at all three time points was associated with significantly improved PFS, and MRD^neg at Y1 had significantly longer OS. Multivariate analysis of PFS, adjusting for disease risk and treatment arm, demonstrated hazard ratios (HRs) in MRD-positive patients compared with MRD^neg patients at BL, PM, and Y1 of 1.55 (<i>P</i> = .0074), 1.83 (<i>P</i> = .0007), and 3.61 (<i>P</i> < .0001), respectively. Corresponding HRs for OS were 1.19 (<i>P</i> = .48), 0.88 (<i>P</i> = .68), and 3.36 (<i>P</i> < .001). Patients with sustained MRD^neg or who converted to MRD^neg by Y1 had similar PFS/OS. To our knowledge, this first, prospective US cooperative group, multicenter study demonstrates that MRD^neg at Y1 after AutoHCT with lenalidomide maintenance is prognostic for improved 6-year PFS and OS. Serial MRD measurements may direct trials to test how further therapy may improve long-term PFS and OS.