Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma

Guidelines for monitoring multiple myeloma (MM) patients expressing light chains only (light-chain MM [LCMM]) rely on measurements of monoclonal protein in urine. Alternatively, serum free light chain (sFLC) measurements have better sensitivity over urinemethods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here, we compared performance of serum and urine measurements in 113 (72 kappa, 41 lambda) newly diagnosed LCMM patients enrolled in the Intergroupe Franco-phone du Myelome (IFM) 2009 trial. All diagnostic samples (100%) had an abnormal k:lambda sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (>= 100 mg/L). By contrast, only 64% patients had measurable levels of monoclonal protein (>= 200mg per 24 hours) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in71% and46% of patients, respectively, whereas UPEP reported a positive result in 37% and 18%; all of the patients with positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal k:lambda sFLC ratio after 3 treatment cycles associated with poorer progression-free survival (P =.006 and P < .0001, respectively), whereas positive UPEP or urine immunofixation electrophoresis (uIFE) did not. In addition, patients with an abnormal k:lambda sFLC ratio had poorer overall survival (P = .022). Finally, early normalization of k:lambda sFLC ratio but not negative uIFE predicted achieving negative minimal residual disease, as determined by flow cytometry, after consolidation therapy (100% positive predictive value). We conclude that improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients.