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Reference: (N Engl J Med 2013 Aug 1;369(5):438), (level 2 [mid-level] evidence)
Standard care for patients with smoldering (asymptomatic) myeloma is observation for emergence of myeloma-related organ impairment with monitoring of serum and urine paraprotein levels. The risk of disease progression is generally low (about 10% annually over the first 5 years) (N Engl J Med 2002 Feb 21;346(8):564), and guidelines recommend chemotherapy only in cases of symptomatic myeloma-related organ impairment (Br J Haematol. 2011 Jul;154(1):32). However, in a sizeable subpopulation of asymptomatic patients with greater bone marrow infiltration, the risk of progression is increased. A recent unblinded randomized trial evaluated the efficacy of early treatment in 125 patients with high-risk smoldering myeloma.
Patients aged 38-91 years with high-risk smoldering myeloma (43% with diagnosis within 6 months) were randomized to early treatment vs. observation. Early treatment consisted of induction with lenalidomide 25 mg/day on days 1-21 plus dexamethasone 20 mg/day on days 1-4 and 12-15 every 4 weeks for 9 cycles, followed by maintenance therapy with lenalidomide 10 mg/day on days 1-21 every 4 weeks for 2 years. High-risk disease was defined as either plasma-cell bone marrow infiltration ≥ 10% plus a monoclonal component (IgG level ≥ 3 g/dL, IgA level ≥ 2 g/dL, or urinary Bence Jones protein level >1 g/day) or 1 of these criteria plus ≥ 95% phenotypically aberrant plasma cells in the bone marrow plasma cell compartment with ≥ 25% decrease in 1-2 uninvolved immunoglobulins.
After median follow-up of 40 months, early treatment was associated with longer time to progression than observation (hazard ratio for progression 0.18, p < 0.001). The median time to progression was not reached in the early treatment group (i.e. fewer than half the group had progression during follow-up), vs. 21 months in the observation group . Early treatment was also associated with significantly higher 3-year survival (94% vs. 80%, p = 0.03, NNT 8). In the early treatment group, at least partial response was observed in 79% during the induction phase and 90% during maintenance.
For more information, see the Multiple Myeloma topic in DynaMed.