MRD Versus Stringent Complete Response to Predict Outcomes in Multiple Myeloma

In a head-to-head comparison of minimal residual disease (MRD) versus stringent complete response (sCR) to determine clinical response in patients with multiple myeloma (MM), researchers found that sCR does not predict a different outcome, and more sensitive techniques are able to identify patients with differing prognoses. “We suggest that MRD categories should be implemented over sCR for the future classification of MM responses,” the researchers wrote of the findings, which were published in PLoS One.

Researchers used a four-color multiparametric flow cytometry (MFC) or next-generation sequencing (NGS) of immunoglobulin genes to analyze and compare the prognostic impact of sCR and MRD monitoring. The study included 193 patients treated at Hospital 12 Octubre in Madrid or the University of California, San Francisco between 2003 and 2018 who achieved CR; patients had both bone marrow aspirates and biopsies available.

Eighty percent of patients were transplant-eligible, and a similar number received some type of maintenance therapy, most commonly lenalidomide. Median follow-up was 27 months. A total of 161 BM samples from 130 patients were analyzed with both immunohistochemistry (IHC) and MFC, whereas 98 bone marrow samples were analyzed with both IHC and NGS of immunoglobulin genes.

Neither serum free light chain ratio clonality by IHC nor plasma cell bone marrow infiltration identified CR patients at distinct risk. Among 162 patients not showing clonality by IHC and 131 showing clonality, the progression-free survival (PFS) outcomes were similar (106 vs. 122 months; P=0.5). Patients with less than 5% of plasma cells by cytology had the same PFS as those with more than 5% (89 vs. 114 months; P=0.6). Patients with sCR had slightly longer PFS.

Patients with negative MFC results had superior outcomes to patients failing to reach MRD negativity (PFS, not available [NA] vs. 53 months; P=0.02). Patients MRD-negative by NGS had superior outcomes to patients failing to reach MRD negativity (PFS, NA vs. 38 months; P=0.0001).

“Our results confirm that response assessment according to the sCR criteria does not predict a different outcome for [patients with] MM with CR. However, more sensitive techniques, including both MFC and NGS of immunoglobulin genes, might identify patients with different prognoses, even among patients with sCR. These results confirm our previous findings and strengthen our suggestion that the sCR category should be rethought for the future classification of MM response,” the researchers concluded.