Smoldering multiple myeloma requiring treatment: time for a new definition?

Abstract

Smoldering multiple myeloma (SMM) bridges the gap between monoclonal gammopathy of undetermined significance (a mostly premalignant disorder) and active multiple myeloma (MM). Until recently, no interventional study in patients with SMM showed improved overall survival (OS) with therapy as compared with observation. A report from the PETHEMA-GEM (Programa Español de Tratamientos en Hematologica) group described both fewer myeloma-related events and better OS among patients with high-risk SMM who were treated with lenalidomide and dexamethasone. This unique study prompted us to review current knowledge about SMM and address the following questions: (1) Are there patients currently defined as SMM who should be treated routinely? (2) Should the definitions of SMM and MM be reconsidered? (3) Has the time come when not treating is more dangerous than treating? (4) Could unintended medical harm result from overzealous intervention? Our conclusion is that those patients with the highest-risk SMM (extreme bone marrow plasmacytosis, extremely abnormal serum immunoglobulin free light chain ratio, and multiple bone lesions detected only by modern imaging) should be reclassified as active MM so that they can receive MM-appropriate therapy and the paradigm of careful observation for patients with SMM can be preserved.

Glutamine-derived 2-hydroxyglutarate is associated with disease progression in plasma cell malignancies

“…To date, high-risk SMM patients do not receive treatment until they progress to overt MM and experience end-organ damage (Supplemental Figure 6). This is because, although a number of useful prognostic factors have been identified, there is a lack of accurate and sensitive biomarkers that can preemptively identify high-risk SMM (26). Being able to identify patients with high-risk SMM will provide an opportunity for changing the treatment paradigm to develop effective preventive and early treatment strategies for MM.…”

Impact of Initial FDG-PET/CT and Serum-Free Light Chain on Transformation of Conventionally Defined Solitary Plasmacytoma to Multiple Myeloma

“…A study recently demonstrated that high-risk SMM seemed to highly benefit from early treatment approach in terms of prolonged TTMM and more importantly OS, rather than to wait for development of symptomatic MM to start treatment (20). The definition of early MM remains debatable, and whether all currently defined high-risk SMMs are early MM, remains however an important matter of debate (21). Similarly, an early treatment for SP should only be proposed to patients identified as being at higher risk, through well-defined prognostic risk factors.…”

The Singapore Myeloma Study Group Consensus Guidelines for the management of patients with multiple myeloma

“…(3) Recent data showed that a subset of patients who lacked organ damage and were classifi ed as SMM according to the previous IMWG criteria have active disease that may benefi t from treatment. (4,5) The IMWG has updated its defi nition of MM to take these changes into account. (6) The following are the key changes made in the 2014 IMWG consensus on diagnosis of MM:…”