Minimal Residual Disease Assessed by Multiparameter Flow Cytometry in Multiple Myeloma: Impact on Outcome in the Medical Research Council Myeloma IX Study

Abstract

MRD assessment by MFC was predictive of overall outcome in patients with myeloma undergoing ASCT. This predictive value was seen in patients achieving conventional CR as well as patients with favorable and adverse cytogenetics. The effects of maintenance strategies can also be evaluated, and our data suggest that maintenance thalidomide can eradicate MRD in some patients.

The current status of minimal residual disease assessment in myeloma

“…[5][6][7] Despite this level of response, studies have shown that the vast majority of patients have residual tumor cells that can be detected with a variety of sensitive techniques. [8][9][10][11] Several studies have demonstrated a consistent improvement in progression-free survival (PFS) with attainment of CR, but its impact on overall survival (OS) has been varied. 12,13 The impact of depth of response on PFS is not surprising, as that could be a mere reflection of the time taken for the clone to grow to a measurable level following a more effective eradication.…”

“…To date two large studies have shown precisely this. 8,10 Both studies have depended on flow cytometry-based detection of tumor cells to define the MRD, but other studies have used ASO-PCR-based approaches for MRD detection. In the current issue of Leukemia, Puig et al 9 present a comparative study examining the two techniques side by side.…”

“…These, along with the required expertise and the more universal access to flow cytometry in most of hematology laboratories, makes flow cytometry the method of choice today, and increasing ability to interrogate millions of cells in a short time and increasing number of markers that can be accommodated at a time will lead to increasing sensitivity, specificity and ease of use of this technique. 8,10 However, there is still a lack of uniformity in the cell processing methodology, specific markers required, the minimum number of cells to be studied and gating approaches that have hampered universal adoption of the technique. 14 The European Myeloma Network has developed a consensus on the approach, which has been utilized in the recent MRC study and defines an aberrant phenotype as a lack of CD19 expression, strong CD56 expression, weak CD27 expression and/or weak CD45 expression.…”

“…15 In patients with few events, additional markers such as CD81, CD117, CD200 and/or CD52 can be useful. 8 We have found the use of light chain restriction as an important adjunct to the use of the above set of markers. 16 Another missing piece in this puzzle is what to do with the information regarding MRD status.…”

“…The recent MRC study of MRD also appears to substantiate this. 8 So there is clearly a tipping point where the cost of therapy (financial and quality of life) justifies the goal of achieving MRD negativity, and is likely determined by the disease biology. This question is likely to require prospectively designed studies utilizing responseadapted therapy strategies that also incorporates biological risk stratification methods.…”