MRD Status a Superior Predictor of PFS in Multiple Myeloma?

Minimal residual disease (MRD) as measured by flow cytometry and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) predicted improved progression-free survival (PFS) better than standard risk factors among patients with multiple myeloma, according to a study published in Cancer.

In addition, treatment with maintenance lenalidomide further increased the rate of MRD negativity among this patient population.

Manuela Gambella, MSc, of University of Torino, Turin, Italy, and colleagues conducted the study in 73 patients with newly diagnosed disease enrolled in two clinical trials (RV-MM-EMN-441 and RV-MM-COOP-0556). Patients had all achieved a very good partial response and were assigned to lenalidomide maintenance until disease progression. MRD was evaluated after 6 courses of maintenance therapy and every 6 months until clinical relapse using both MFC and ASO-RC-PCR.

Prior to initiating maintenance therapy, 46% of patients had achieved a molecular complete response and 63% had achieved a flow complete response. Having achieved negative MRD after intensification/consolidation resulted in a significantly better PFS compared with MRD-positive status when analyzed by ASO-RQ-PCR (not reached vs 37.1 months; P = .01) and by MFC (not reached vs 26 months; P = .002).

The median duration of maintenance therapy was about 2.5 years. Among those patients who were MRD-positive at maintenance initiation, 31% obtained a molecular complete response and 23% achieved a flow complete response. Almost 27% of patients who were MRD-positive after consolidation achieved MRD-negative status during maintenance.

Compared with the use of baseline prognostic factors for myeloma, negative MRD status was the most significant factor to reduce risk for progression or death using both evaluation methods (ASO-RQ-PCR, HR = 0.29, P = .001; MFC, HR = 0.19, P < .01).

“It is noteworthy that MRD-negative patients with high-risk cytogenetics had prolonged PFS (median, not reached by either ASO-RQ-PCR or MFC) vs MRD-positive patients (median, 22.6 months by

ASO-RQ-PCR, 15.4 months by MFC),” the researchers wrote. “This observation is in line with data from a Spanish study in which the presence of baseline high-risk cytogenetic features and persistent MRD at day 100 after transplantation were associated with early relapse.”

Comparing the two evaluation methods, MFC and ASO-RQ-PCR had highly significant levels of concordance for MRD analysis (P < .001). Of the 317 samples analyzed by both methods, there was concordance in 90%.

The researchers noted that newer techniques like next-generation sequencing can overcome some of the limitations of MFC and ASO-RQ-PRC, and are now accepted as standardized MRD assessment procedures.