Monoclonal proteinuria predicts progression risk in asymptomatic multiple myeloma with a free light chain ratio ≥100.

A baseline involved to uninvolved free light chain ratio (FLCr) ≥100 with involved FLC ≥10 mg/dL is a multiple myeloma (MM)-defining event (MDE). However, multimeric light chain aggregates may contribute to increased FLC levels and impair renal light chain clearance. Therefore, we conducted a retrospective study to assess the association between urine monoclonal protein (uMCP) excretion and the risk of progression. We included 822 asymptomatic MM patients without MDE besides elevated FLCr (n=120 with FLCr ≥100, n=702 with FLC <100). Patients with a FLC ≥100 were grouped based on 24-hour uMCP excretion (≥200 mg/24h [n=35], <200 mg/24h [n=85]). The 2-year risk of progression to symptomatic MM or AL amyloidosis was significantly higher in patients with uMCP excretion ≥200 versus <200 mg/24h (36.2% versus 13.5%, respectively; HR 2.79, 95%CI 1.57-4.96, p<0.001). However, the progression risk was similar in patients with a baseline FLCr <100 versus FLC≥100 with uMCP <200 mg/24h (log rank p=0.127). We showed that increased uMCP excretion in the setting of a FLCr ≥100 is an unfavorable prognostic marker. This underscores the importance of conducting a diagnostic 24-hour urine assessment and may help refine the subset of patients warranting therapy if the FLCr is the only MDE.