Association of MRD Status With Outcomes After Autologous Stem Cell Transplantation for Multiple Myeloma

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In an analysis from the UK phase III MYELOMA XI trial reported in the Journal of Clinical Oncology, de Tute et al found that persistent measurable residual disease (MRD)-negative status after autologous stem cell transplantation (ASCT) and conversion from MRD-positive to -negative status were associated with improved survival outcomes in patients with multiple myeloma.

Study Details

In the trial, patients who underwent ASCT were randomly assigned to receive lenalidomide maintenance therapy or observation at 3 months after ASCT. Patients were assessed for MRD (median sensitivity = 0.004%) prior to random assignment at 3 months and at 9 months after ASCT.

Key Findings

Among patients with MRD status available at 3 months, 475 (63.3%) of 750 were MRD-negative and 275 (36.7%) were MRD-positive. Median progression-free survival for the MRD-negative group vs the MRD-positive group was 44 vs 24 months (hazard ratio [HR] = 0.47, 95% confidence interval [CI] = 0.37–0.58, P < .0001). Overall survival at 3 years was 86.5% vs 78.7% (HR = 0.59, 95% CI = 0.40–0.85, P = .0046).

At 9 months after ASCT, 214 (65.6%) of 326 patients were MRD-negative and 112 (34.4%) were MRD-positive. Median progression-free survival was 50 vs 13 months (HR = 0.20, 95% CI = 0.13–0.31, P < .0001). Overall survival at 3 years was 86.9% vs 69.5% (HR = 0.33, 95% CI = 0.15–0.75, P = .0077).

Sustained MRD negativity from 3 to 9 months or conversion from MRD positivity to MRD negativity at 9 months were associated with the longest progression-free survival (median = 50 months and not estimable) and overall survival (3-year rates of 81.5% and 100%). Conversion to MRD-negative status was more common in the lenalidomide maintenance group vs the observation group (30% vs 17%).

High-risk molecular features were associated with poorer progression-free and overall survival, including among patients with MRD-negative status.

On multivariate analysis:

  • MRD-negative status was significantly associated with improved progression-free survival and overall survival at 3 months (HRs = 0.40 and 0.46) and 9 months (HRs = 0.22 and 0.24)
  • Lenalidomide maintenance vs observation was associated with improved progression-free survival and overall survival at 3 months (HRs = 0.39 and 0.53) and progression-free survival and overall survival at 9 months (HRs = 0.22 and 0.25)
  • High molecular risk was associated with poorer progression-free survival and overall survival at 3 months (HRs = 2.58 and 4.29) and at 9 months (HRs = 2.36 and 6.66).

The investigators concluded, “In patients with multiple myeloma, MRD status at both 3 and 9 months after ASCT is a powerful predictor of progression-free and overall survival.”

Roger G. Owen, MD, PhD, of Leeds Cancer Centre, Leeds Teaching Hospitals Trust, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Cancer Research UK. For full disclosures of the study authors, visit

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