Spanish Analysis of Prognostic Impact of MRD-Negative Status in Multiple Myeloma


Key Points

  • In patients with newly diagnosed multiple myeloma, complete response without MRD-negative status was not associated with improved outcomes vs a near-complete or partial response.
  • MRD-negative status was associated with improved progression-free and overall survival vs complete response without MRD-negative status.

A pooled analysis of three PETHEMA/GEM studies has shown that minimum residual disease (MRD)-negative status after induction therapy is more prognostic of favorable outcome than complete response alone in newly diagnosed multiple myeloma. The findings were reported by Lahuerta et al in the Journal of Clinical Oncology.

The study included data from 609 patients from 2 GEM studies in transplant-eligible disease and 1 study in fit elderly patients who had MRD assessment at 9 months after study enrollment. Median follow-up of the pooled population was 71 months.

Impact of MRD-Negative Status

Neither median progression-free survival nor median overall survival differed among patients with complete response without MRD-negative status (27 and 59 months), those with a near-complete response (27 and 64 months) or those with a partial response (29 and 65 months). MRD-negative status was associated with prolonged progression-free survival (median = 63 months, P < .001) and overall survival (median not reached, P < .001) vs complete response without MRD-negative status overall and among subgroups according to prior transplantation, disease stage, and cytogenetics.

Among all patients with a complete response (irrespective of MRD status), hazard ratios were 0.67 for progression-free survival and 0.58 for overall survival compared with patients without a complete response, whereas respective hazard ratios were 0.42 and 0.33 for all patients with MRD-negative vs -positive status (all P < .001). Achievement of a complete response had no significant effect on outcome in patients with high-risk cytogenetics, whereas MRD-negative patients with high-risk cytogenetics (n = 25) had prolonged progression-free survival (median = 38 vs 14 months, P < .001) and overall survival (median = 128 vs 26 months, P < .001) compared with MRD-positive patients (n = 35).

The investigators concluded: “Our results demonstrate that MRD-negative status surpasses the prognostic value of [complete response] achievement for [progression-free and overall survival] across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with [multiple myeloma].”

The study was supported by the Centro de Investigación Biomédica en Red-Area de Oncologia-del Instituto de Salud Carlos III and others.

Jesus F. San-Miguel, MD, PhD, of Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, Pamplona, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.