“In our opinion, patients with time to progression of approximately 2 years could benefit from early therapy, and this has been demonstrated in the QUIREDEX Spanish clinical trial (ClinicalTrials.gov Identifier: NCT00480363), not only in terms of progression-free survival but also in overall survival,” he added.

However, Dr Hernández-Rivas emphasized the growing need to treat another group of patients: those with ultra-high-risk SMM. Based on recommendations from the IMWG, this patient subgroup, defined as demonstrating BMPC percentage of at least 60, sFLC ratio greater than 100, or at least 1 oseous or bone marrow focal lesion on imaging, should be considered to have symptomatic MM and should be treated accordingly. “The ultra-high-risk group of patients with SMM accounts for only 2% to 3% of this population,” Dr Hernández-Rivas said, “and most of the groups follow these recommendations.”

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At the two ends of the SMM spectrum, treatment decisions are better defined. Patients with ultra-high-risk SMM experience a risk of progression greater than 80% at 2 years and are now being considered as candidates for treatment. It is also clear that patients with a prognosis similar to that of MGUS should not receive early intervention. The main controversy, noted the authors, is whether patients with high-risk SMM, whose risk of progression at 2 years is approximately 50%, and patients with intermediate-risk SMM, whose risk of progression at 5 years is 40%, should be treated.

Recent evidence has demonstrated that lenalidomide given with dexamethasone can delay progression to symptomatic MM and increase survival in patients with high-risk SMM. In younger patients, the goal of clinical trials is to achieve very deep responses resulting in delayed progression and prolonged survival, though some researchers are also evaluating the possibility of a cure. Among older patients, trials are looking at drug combinations with the goal of not only prolonging survival but demonstrating a good safety profile.

At the present time, the US Food and Drug Administration and the European Medicines Agency have not approved any treatment schedules for SMM, Dr Hernández-Rivas noted, although some clinicians feel that patients with high-risk SMM should be treated. “The preference is [to treat patients] in a clinical trial but in some cases, doctors are treating these high-risk patients with SMM,” he said. “In our opinion, it is difficult to explain to a patient with high-risk SMM that we will not administer treatment with the evidence available, and it is also ethically questionable. Nevertheless, new clinical trials such as ASCENT (ClinicalTrials.gov Identifier: NCT03289299) or GEM-CESAR (ClinicalTrials.gov Identifier: NCT02415413) could clarify this issue.”


  1. Hernández J-Á, Martínez-López J, Lahuerta J-J. Timing treatment for smoldering myeloma: Is earlier better? [published online April 4, 2019]. Expert Rev Hematol. doi:10.1080/17474086.2019.1599281

This article originally appeared on Hematology Advisor