Immunoglobulin heavy light chain test quantifies clonal disease in patients with AL amyloidosis and normal serum free light chain ratio

<i>Background</i>: Serum and urine immunofixation electrophoreses (SIFE/UIFE) are used for clonal detection in plasma cell dyscrasias, while serum free light chain (sFLC) testing provides quantitation of clonal disease. Up to 20% of patients with light chain (AL) amyloidosis may present with normal FLC ratio (FLCr). <i>Methods</i>: We assessed the diagnostic, quantitative and prognostic potential of serum heavy light chain ratio (HLCr) in 199 untreated patients at initial evaluation. <i>Results</i>: An abnormal HLCr was found in 37.2%, abnormal FLCr in 81.9% and positivity by SIFE/UIFE in 94% of patients. HLCr together with SIFE/UIFE identified clonality in 94% patients; the combination with FLCr yielded 100% sensitivity. An HLCr abnormality was significantly over-represented in normal compared to abnormal FLCr group (63.9% versus 31.3%). HLCr did not predict overall survival (OS) (log rank, <i>p </i>=<i> </i>0.09), while an abnormal FLCr was associated with decreased OS (log rank, <i>p </i>=<i> </i>0.03). The combined use of both ratios trended toward increased OS in the abnormal HLCr/normal FLCr group (log rank, <i>p </i>=<i> </i>0.11; Wilcoxon, <i>p </i>=<i> </i>0.04). On multivariate analysis, HLCr was not predictive of OS, whereas an abnormal FLCr was associated with shorter OS (HR = 1.7, <i>p </i>=<i> </i>0.04). <i>Conclusions</i>: The HLC assay has potential as a supplemental test to quantify monoclonal protein in patients with normal FLCr results.