Kumar et al.  noted that AL amyloidosis patients had a worse survival if there was no intact monoclonal immunoglobulin detectable (12.6 months vs 29.3 months, p=0.02). The patients without monoclonal heavy chain had a higher dFLC value (255 vs 153 mg/L, p<0.001) but on multivariate analysis both dFLC and the presence/absence of heavy chain were independently prognostic for survival. Kumar et al.  also reported that AL amyloidosis patients with high sFLC burden (dFLC >196 mg/L), had more frequent and severe cardiac involvement, with higher levels of cardiac biomarkers troponin T (cTnT) and pro-B-type natriuretic peptide (NT-ProBNP) . However, in a multivariate analysis that included a variety of markers, baseline dFLC remained an independent predictor of survival. In a subsequent publication from the same centre , a revised staging system for AL amyloidosis was proposed incorporating dFLC alongside the cardiac biomarkers cTnT and NT-ProBNP. Patients were assigned a score of 1 for each of the following: 1) dFLC ≥180 mg/L; 2) cTnT ≥0.025 ng/mL or, 3) NT-ProBNP ≥1800pg/mL, to give stages I to IV (for 0 - 3 points, respectively). The staging system was derived from 810 patients with newly diagnosed AL amyloidosis and tested on two further populations (n=303 and n=103). The authors concluded that this revised Mayo staging system (based on sFLC measurements and cardiac biomarkers) allowed better discrimination of patient outcomes in AL amyloidosis than a staging system based on cardiac biomarkers alone, and should be incorporated into future clinical trials .
Three independent studies have characterised the subgroup of AL amyloidosis patients who do not have measurable disease by sFLCs at diagnosis (dFLC <50 mg/L) . This group accounts for 15 - 19% of all newly diagnosed patients, and represents a distinct clinical entity. Milani et al.  reported that such patients are characterised by a lower incidence of heart involvement (43% vs. 83%, p<0.001), higher incidence of renal involvement (77% vs. 63%, p<0.001) that tended to be more severe, with a more favourable outcome compared to with patients with evaluable FLCs (median 117 vs. 21 months, p<0.001). Similar findings were observed by Dittrich et al. . This study also reported lower bone marrow plasma cell counts (6% vs. 10%, p<0.001), smaller M-spikes (7 g/L vs. 9 g/L (p<0.001) and lower concentrations of monoclonal heavy chain (7 g/L vs. 10 g/L, p=0.003) among patients with a dFLC <50 mg/L. It has been suggested that such patients are underrepresented in clinical studies, because their haematologic response cannot be reliably measured, which may adversely influence results . However, Milani et al.  have demonstrated a survival benefit for patients with a low dFLC burden who subsequently achieve a complete response, and proposed that these patients can be included in clinical trials with appropriate stratification and be evaluated for complete response.
Wassef et al.  used the above staging system when comparing sFLC results produced by Freelite with another manufacturer's monoclonal antibody-based FLC assays. The quantitative results and stage allocation differed for the two immunoassays, indicating that the staging system cannot be extended to different assays without separate validation (Chapter 8).