Abstract
ObjectiveIn clinical trials (CTs), the assessment of minimal residual disease (MRD) has proven to have prognostic value for multiple myeloma (MM) patients. Multiparameter flow cytometry (MFC) and next-generation sequencing are currently used in CTs as effective tools for outcome prediction. We have previously described 6- and 8-color MFC panels with and without kappa/lambda, which were equally reliable in detecting aberrant plasma cells (aPC) in myeloma bone marrow (BM) specimens. This follow-up study a) established a highly sensitive single-tube 10-color MFC panel for MRD detection in myeloma samples carrying different disease burden (monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM), MM), b) evaluated additional, rarely used markers included in this panel, and c) assessed MRD levels and the predictive value in apheresis vs. BM samples of MM patients undergoing autologous stem cell transplantation (ASCT).Methods + ResultsThe 10-color MFC was performed in BM and apheresis samples of 128 MM and pre-MM (MGUS/SMM) patients. The markers CD28, CD200, CD19, and CD117 underwent closer examination. The analysis revealed distinct differences in these antigens between MM, MGUS/SMM, and patients under treatment. In apheresis samples, the 10-color panel determined MRD negativity in 44% of patients. Absence of aPC in apheresis corresponded with disease burden, cytogenetics, and response to induction. It also determined MRD negativity in BM samples after ASCT and was associated with improved progression-free survival.ConclusionThese results highlight the significance of the evaluation of both BM and apheresis samples with a novel highly sensitive 10-color MFC panel.
Highlights
Multiple myeloma (MM) is characterized by the accumulation of aberrant plasma cells in the bone marrow (BM)
We have previously described 6- and 8-color multiparameter flow cytometry (MFC) panels with and without kappa/lambda, which were reliable in detecting aberrant plasma cells in myeloma bone marrow (BM) specimens
We investigated the effectiveness of additional markers (i.e., CD200, CD81, CD28, and CD117) at pre-MM stage (MGUS/ smoldering multiple myeloma (SMM)), at initial diagnosis of MM (ID), during disease progression (PD), under anti-MM treatment, and whether they could provide a similar or increased reliability in identification of aberrant plasma cells (aPC) compared to kappa/lambda
Summary
Multiple myeloma (MM) is characterized by the accumulation of aberrant plasma cells (aPC) in the bone marrow (BM). While NGS has the advantage of better performance on limited cell numbers, MFC provides results within hours, does not require a baseline sample, and is applicable to nearly 100% of patients [8]. The establishment of this method in MRD detection has largely been advanced by the EuroFlow consortium [9]. The comparison of the 6-color panel and the 8-color panel has already been published and showed that both panels with and without kappa/lambda were robust and reliably detected aPC and normal plasma cells (nPC), with kappa/ lambda being an additional tool for assessing clonality [10]. In this paper, we focused on the evaluation of potential benefits and disadvantages of the 10-color panel
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