Longitudinal Flow Cytometry Identified "Minimal Residual Disease" (MRD) Evolution Patterns for Predicting the Prognosis of Patients with Transplant-Eligible Multiple Myeloma

Background: Many questions about "minimal residual disease" (MRD) still need to be answered for multiple myeloma (MM). Methods: Flow MRD were monitored in 104 consecutive patients with MM after induction and at the 3^rd, 6^th, 9^th, 12^th, 18^th, and 24^th months post-transplant. Results: Four MRD evolution patterns were revealed: pattern 1 patients had persistent MRD-negative after post-induction with no progression; pattern 2 patients had MRD-positive status post-induction but became MRD negative within 24 months post-transplant; pattern 3 patients had MRD-negative post-induction but became MRD-positive within 24 months post-transplant; and pattern 4 patients had persistent MRD-positive after post-induction. Patients with MRD evolution pattern 1 had a better time to progression (TTP) than did the patients with the other evolution patterns (not reached vs. not reached, vs. 15.4 ± 2.4 months, vs. 16.9 ± 3.0 months; log-rank test, p=0.003, 0.000, 0.000). Patients with MRD pattern 1 had a significantly longer OS than did patients with pattern 3 (not reached vs. 35.2 ± 18.6 months; log-rank test, p=0.000) and pattern 4 (not reached vs. 23.8 ± 15.0 months, log-rank test, p=0.000), but had a similar OS as did pattern 2 patients (not reached vs. not reached; log-rank test, p=0.229). For progressing patients with MRD evolution pattern 2 or 3, the median interval of a sustained MRD-negative status was only 17 months and the median time from MRD reappearance to disease progression was only 4.6 months. Conclusions: (1) A more complete MRD evolution pattern was developed to predict the outcomes for patients with MM. (2) The optimal time of MRD assessment should include post-induction, 3^rd month and 24^th month post-transplant. (3) Regular MRD assessments will help detect relapse early. (4) A sustained negative MRD status should last for at least 24 months.