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

Purpose: 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).

Methods: 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).

Results: 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 (P = .0074), 1.83 (P = .0007), and 3.61 (P < .0001), respectively. Corresponding HRs for OS were 1.19 (P = .48), 0.88 (P = .68), and 3.36 (P < .001). Patients with sustained MRD^neg or who converted to MRD^neg by Y1 had similar PFS/OS.

Conclusion: 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.

Figure 1:

Baseline MRD status with progression-free (A) and overall survival (B) and Pre-Maintenance MRD status with progression-free (C) and overall survival (D) Panels A and B have the observation time Year 0 starting at date of autologous transplant; Panels C and D have the observation time Year 0 starting at the date of the pre-maintenance MRD assessment.

Figure 2:

One-Year MRD status with progression-free (A) and overall survival (B) and Sustained vs Converted MRD negative at one-year after autologous transplant with progression-free (C) and overall survival (D) Panels A through D have the observation time Year 0 starting at the date of the 1-year post-transplant MRD assessment.

Figure 3:

Multivariate analysis of A) Progression-Free and B) Overall Survival