MRD Has Prognostic Value in Elderly Myeloma Patients

Monitoring of minimal residual disease (MRD) in a group of elderly patients with multiple myeloma proved to have important prognostic value, regardless of patient age or cytogenetic risk, according to the results of a study published in Blood.

The study used second-generation 8-color multiparameter-flow-cytometry (MFC) to monitor MRD in 162 patients who were ineligible for transplant enrolled in the PETHEMA/GEM2010MAS65 study. Patient MRD status was an independent prognostic factor for time to progression and overall survival.

“The availability of highly effective therapies for elderly multiple myeloma patients urges the need to address if response-driven (ie, MRD-based) treatment decisions can reduce the difference in survival between transplant eligible and elderly patients (or even standard- vs high-risk multiple myeloma),” wrote researcher Bruno Paiva, PhD, of Instituto de Investigacíon Sanitaria de Navarra, Pamplona, Spain, and colleagues. “This requires a cooperative effort toward novel clinical trial designs in which patients are accurately stratified according to sensitive MRD monitoring prior to alternative treatment strategies, or even randomized into different therapeutic approaches according to MRD status.”

The researchers used this second generation MFC to identify three patient groups in the study: MRD negative (< 10^-5; n = 54, 34%), MRD positive (between < 10^-4 and 10^-5 or greater; n = 20, 12%), and MRD positive (greater than or equal to 10^-4; n = 88, 54%).

First, MRD status was assessed after the first 9 cycles of chemotherapy. At that time, 20% of patients were MRD negative and these patients had significantly prolonged time to progression and improved overall survival compared with patients in complete response but with MRD-positive disease. Next, the researcher evaluated MRD at cycle 18. At that time, 19% of patients who were MRD-positive at cycle 9 had become MRD negative; however, no MRD-negative cases at cycle 9 turned to MRD-positive cases.

A multivariate analysis that included baseline and post-treatment disease features showed that MRD status was an independent prognostic factor for time to progression (hazard ratio [HR], 2.7; P = .007), and overall survival (HR, 3.1; P = .04). Patients who were classified as MRD negative had a significant benefit with a 70% overall survival at 3 years and a median time to progression not yet reached.

The researchers also found that having MRD-negative status significantly improved time to progression among patients older than 75 (HR, 4.8; P < .001) and those with high-risk cytogenetics (HR, 12.6; P = .01).

“The clinical significance of our results is twofold: (1) MRD-positive patients should be considered as candidates for further (alternative) therapies in order to control chemoresistant plasma cells, and (2) the definition of complete remission would also benefit elderly patients by incorporating MRD assessment into the response criteria,” the researchers wrote. “In this regard, sequential MRD monitoring would be particularly attractive to identify patients with sustained MRD negativity; accordingly, herein the best outcome was noted among the 18 MRD-negative cases at both cycles 9 and 18.”