MRD Negativity Is Critical for Prolonged Remissions in High- and Standard-Risk MM

Patients with high-risk multiple myeloma often experience early relapses and poorer survival than lower-risk patients. However, the degree of minimal residual disease (MRD) in this patient population prior to relapse is unknown. This study seeks to assess the impact of molecular negativity by MRD assessment in patients who have achieved at least very good partial response (VGPR) or complete response (CR) at 4 to 8 months (following autologous stem-cell transplant [ASCT]) and 12 to 24 months maintenance therapy after enrollment.

In this study, 91 patients were identified who achieved at least VGPR and had bone marrow samples available at 4 to 8 months and 12 to 24 months after enrollment. Of these patients, 14 had high-risk disease and 77 had lower-risk disease. Of the 14 patients with high-risk disease, 6 were MRD-negative and 8 were MRD-positive at baseline. Of these patients, 1 MRD-negative patient became MRD-positive, and 1 MRD-positive patient was MRD-negative after 12 to 24 months. In the low-risk group of 77 patients, 1 of the 23 MRD-negative patients became MRD-positive after 12 to 24 months, and 25 of the 54 MRD-positive patients were MRD-negative after 12 to 24 months.

The results indicated that there was no significant difference for progression-free survival and overall survival (OS) at 4 to 8 months between MRD-positive and MRD-negative patients. However, patients who were MRD-negative at 12 to 24 months had a significant OS benefit compared to MRD-positive patients. Fifty-one patients in the initial group of 91 patients continue to be in complete remission to date >6 years after enrollment. All but 3 of these patients are MRD negative.

These data suggest that patients achieving MRD-negative status after ASCT are less likely to have a clinical relapse and are more likely to have a favorable outcome after 24 months.