Figure 2.
Dissecting Mayo Clinic retrospective data from smoldering multiple myeloma to multiple myeloma: 3 patterns of clinical trajectory. When the patterns of progression from smoldering multiple myeloma to multiple myeloma in the retrospective Mayo Clinic study are looked at (A),6 as discussed in detail in the text, in my opinion, this definition is highly clinically heterogeneous, and it could be dissected into 3 main clinical patterns: multiple myeloma with early detection (B), indolent multiple myeloma (C), and monoclonal gammopathy (D). That patients with early detection multiple myeloma, typically, develop multiple myeloma within 1 to 2 years indicates that they have the same disease as patients with multiple myeloma, just at an earlier stage.7,19 As discussed in the text, to me, it seems logical to propose that the clinical implication of these arguments is that patients with high-risk smoldering multiple myeloma should be moved into the definition of multiple myeloma so they can be offered access to active therapy. Regarding the role of early treatment in the group of patients with indolent multiple myeloma, it is less obvious to form strategies. Reviewing the literature on indolent lymphomas,33 for example, early intervention vs delayed intervention (eg, at rising biomarkers) are both options that may be proposed. We need properly designed clinical trials to obtain answers on optimal management of indolent multiple myeloma. Also as discussed in detail in the text, with new data that link the precursor and multiple myeloma together,18 the “uncertain significance” (ie, MGUS) terminology seems no longer relevant. To me, it seems reasonable to propose the terminology “monoclonal gammopathy” for current patients with MGUS and patients with low-risk smoldering multiple myeloma. To caution the reader and to avoid confusion in the clinical field, before going forward, these ideas and concepts will have to be agreed on and endorsed in a consensus document. The intent is to share expert opinions based on clinical experience and original data, beyond the regular text book. The hope is to stimulate the reader to approach the current paradigm in a critical manner and to facilitate avenues for new translational research. Panel A is adapted from Kyle et al.6