Serum free light chains should be the target of response evaluation in light chain multiple myeloma rather than urines.
(2016) Blood — Vol. 128, n° 25, p. 1941-2948 (2016)
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- Guidelines for monitoring multiple myeloma patients expressing light chains only (light chain multiple myeloma; LCMM) rely on measurements of the monoclonal protein in urine. Alternatively serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here we compared the performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled onto the IFM-2009 trial. All diagnostic samples (100%) had an abnormal κ/λ sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (≥100mg/L). By contrast, only 64% patients had measurable levels of the monoclonal protein (≥200mg/24h) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in 71% and 46% patients, respectively, whilst UPEP reported a positive result in 37% and 18%; all the patients with a positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal κ/λ sFLC ratio after 3 treatment cycles associated with poorer PFS (p=0.006 and p<0.0001, respectively), whereas positive UPEP or urine immunofixation (uIFE) did not. In addition, patients with an abnormal κ/λ sFLC ratio had poorer overall survival (p=0.022). Finally, early normalisation of κ/λ 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.
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Dejoie, T., Corre, J., Caillon, H., Hulin, C., Perrot, A., Caillot, D., Boyle, E., Chretien, M.-L., Fontan, J., Belhadj, K., Brechignac, S., Decaux, O., Voillat, L., Rodon, P., Fitoussi, O., Araujo, C., Benboubker, L., Fontan, C., Tiab, M., et al. (2016). Serum free light chains should be the target of response evaluation in light chain multiple myeloma rather than urines. Blood, 128(25), 1941-2948. https://doi.org/10.1182/blood-2016-07-726778 (Original work published 2016)