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

Abstract

Many questions about minimal residual disease (MRD) still need to be answered for multiple myeloma (MM). Flow MRD was monitored in 104 consecutive patients with MM after induction and at the 3rd, 6th, 9th, 12th, 18th, and 24th months post-transplant. Four MRD evolution patterns were revealed: Pattern 1 patients had persistent MRD-negative status after post-induction with no progression; pattern 2 patients had MRD-positive status postinduction but became MRD negative within 24 months post-transplant; pattern 3 patients had MRD-negative status postinduction but became MRD positive within 24 months post-transplant; and pattern 4 patients had persistent MRD-positive status after postinduction. Patients with MRD evolution pattern 1 had a better time to progression than did patients with the other evolution patterns (not reached versus not reached, versus 15.4 ± 2.4 months, versus 16.9 ± 3.0 months; log-rank test, P = .003, P = .000, and P = .000, respectively). Patients with MRD pattern 1 had a significantly longer overall survival than did patients with pattern 3 (not reached versus 35.2 ± 18.6 months; log-rank test, P = .000) and pattern 4 (not reached versus 23.8 ± 15.0 months, log-rank test, P = .000) but had a similar overall survival as pattern 2 patients (not reached versus not reached; log-rank test, P = .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. A more complete MRD evolution pattern was developed to predict the outcomes for patients with MM. The optimal time of MRD assessment should include postinduction and 3rd and 24th month post-transplant. Regular MRD assessments will help detect relapse early. A sustained negative MRD status should last for at least 24 months.

Clinical Applications and Future Directions of Minimal Residual Disease Testing in Multiple Myeloma

“…Data clearly show that, as we continue to intensify patient treatment, the percentage of MRD-negative patients increases (39,43,53,55,56) and even maintenance treatment can convert a significant percentage of MRD-positive patients into MRDnegative [e.g., 27-30% with lenalidomide maintenance in a pooled analysis (9,46)]. Each timepoint can be important due to different clinical reasons.…”

Expression of interleukin-32 in bone marrow of patients with myeloma and its prognostic significance

“…Furthermore, several retrospective studies have demonstrated the value of MRD in predicting early MM recurrence and assessing patient outcomes, it is expected to guide patient follow-up[22,23]. A recent study by Gu et al[24] showed that patients in CR with persistently positive MRD have a higher early recurrence rate and significantly shorter PFS and OS, as compared with CR patients with negative MRD. Another study on MM prognosis also showed that the effect of MRD on PFS and OS in patients is irrelevant in terms of disease stage, induction treatment plan, cytogenetic risk stratification and routine CR, which is significantly better than the traditional efficacy evaluation system[25].…”

Minimal Residual Disease Assessment Within the Bone Marrow of Multiple Myeloma: A Review of Caveats, Clinical Significance and Future Perspectives

“…Second, the frequency of assessment and its longitudinal development, which usually includes post-induction, third and 24th month post-transplant. Third, the setting of patients, as most studies involved patients evaluated after first induction and at different timepoints (within 24 months) post-transplant (55, 56). As expected, consolidation and maintenance can further improve the depth of response and the frequency of MRD negativity (23, 24, 56–58).…”

“…However, patients, who achieved MRD negativity sooner, have better outcomes, as compared to those who became MRD-neg later, after ASCT (28). Low MRD levels correlate to longer PFS, with progressive MRD log-reduction at different timepoints (after either induction, single or double ASCT) (55, 57). However, controversial results have been reported in patients with unfavorable cytogenetic risk, who might either benefit (57–59) or not (46) from MRD negativity achievement (Supplementary Table 1) (60), even if these results might be the consequence of different time of MRD assessment.…”