MRD Status May Outweigh Cytogenetic Risk as Prognostic Marker for Myeloma

Minimal residual disease (MRD) negativity measured by next-generation sequencing was a valuable prognostic biomarker for multiple myeloma, according to a recent study.

“As a result of major improvements in clinical outcomes in recent years, the search for surrogate markers that enable early prediction of survival endpoints and reduce the time required to evaluate new treatments has become a major objective for the myeloma community,” wrote Aurore Perrot, MD, PhD, of University Hospital in Nancy, France, and colleagues, in Blood. “MRD is one of the most promising such biomarkers identified to date.”

Multiple studies are evaluating the use of MRD as a surrogate endpoint in clinical trials in order to shorten evaluation times of novel treatments for myeloma.

In this study, Perrot and colleagues measured MRD during maintenance therapy using next-generation sequencing. This approach, researchers wrote, “demonstrated a higher level of discrimination than had previously been achieved with the less sensitive multiparametric flow cytometry technique.”

MRD was evaluated based on data from a recent clinical trial that looked at transplantation in newly diagnosed myeloma patients treated with lenalidomide, bortezomib, and dexamethasone (RVD). MRD negativity was defined as absence of tumor plasma cells within 1 million bone marrow cells.

One in four patients achieved MRD negativity at least once during maintenance treatment. This percentage was lower in the RVD-alone arm (20%) and higher in the transplantation arm (30%).

The median duration of follow-up was 38 months from the completion of maintenance therapy. At the beginning of maintenance, MRD strongly predicted for progression-free survival (adjusted hazard ratio [HR], 0.22; P < .001) and overall survival (adjusted HR, 0.24; P = .001).

MRD negativity was associated with a greater chance of prolonged progression-free survival compared with patients with detectable residual disease. This was true whether patients underwent treatment with RVD or transplant, regardless of cytogenetic risk profile or International Staging System disease stage at diagnosis.

“This finding raises the possibility that achieving MRD negativity may overcome certain adverse risk factors identified at diagnosis,” the researchers wrote. “These results, coupled with the lack of impact of disease stage or cytogenetic risk profile on MRD negativity rates, should be kept in mind when discussing prognoses with patients not only at diagnosis, but also during the different phases of treatment, as their prognosis could be substantially altered by their achieving MRD-negative status.”