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 with an elevated MDE as the only MDE (n = 120 with FLCr ≥100, n = 702 with FLC < 100). Patients with a FLC ≥ 100 were grouped based on 24-h uMCP excretion (≥200 mg/24 h [n = 35], <200 mg/24 h [n = 85]). The 2-year risk of progression to symptomatic MM or light chain (AL) amyloidosis was significantly higher in patients with uMCP excretion ≥200 versus <200 mg/24 h (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/24 h (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-h urine assessment and may help refine the subset of patients warranting therapy if the FLCr is the only MDE.