Sidana et al.  evaluated a risk stratification model based on a combination of haematological and organ responses to assess early treatment benefit in AL amyloidosis. Their study included 875 newly diagnosed AL amyloidosis patients, all of whom had heart (76%), kidney (66%) and/or liver (17%) involvement at diagnosis. After 6 months follow-up, patients were evaluated using a combined score based on hematological response and the number of organs showing a response. The score divided patients into two groups with significantly different outcomes (median overall survival not reached vs. 30 months), and had greater prognostic value than haematological or organ response alone. As the combined score is easily calculated, Sidana et al.  concluded that it can be easily integrated into both clinical trials and everyday clinical practice.
Cordes et al.  analysed survival data for 74 patients who had received HDM/ASCT and concluded that the lowest post-treatment sFLC concentration provided the best indication of those patients who were more likely to survive for >10 years. Tandon et al.  also studied the prognostic value of involved FLC (iFLC) concentrations, in a group of 345 AL amyloidosis patients whose κ/λ sFLC ratio had normalised after initial therapy. Patients who had persistent elevation of iFLC concentrations at two time points (n=111) had a significantly shorter overall survival compared to those whose values normalised (78 months vs. not reached, p<0.0001). A multivariate analysis confirmed that the prognostic value of elevated iFLCs was independent of renal function.
Palladini et al.  compared response to treatment as assessed by Freelite and the Siemens N Latex FLC assays. Although the results produced by both assays were prognostic, percentage reductions in FLC concentration were quite different, leading the authors to conclude that amended response criteria would be needed for the N Latex FLC assays (Chapter 8).
28.7.1. sFLC response predicting cardiac outcomes
Organ responses are typically slow to appear in patients with AL amyloidosis and are usually dependent on an adequate haematological response. The presence of cardiac amyloidosis is the major prognostic determinant in AL amyloidosis. Although cardiac involvement is present in only approximately half of patients at diagnosis (Section 28.1), virtually all AL amyloidosis patients will die from complications resulting from cardiac dysfunction; patient survival depends on the rapid suppression of monoclonal FLC synthesis and stabilisation or recovery of heart function . Measurement of cardiac biomarkers, namely serum cardiac troponin T and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are useful in defining prognosis at diagnosis (Section 28.4), and should be monitored to assess response to therapy, in parallel with the assessment of haematological response .
The important link between improving cardiac function in AL amyloidosis and falling sFLC concentrations was first observed by Palladini and colleagues . Fifty-one AL amyloidosis patients with symptomatic myocardial involvement were given chemotherapy and monitored with sFLCs and NT-proBNP. During treatment, 22 patients had a reduction of sFLCs by more than 50%, including nine patients who had disappearance of monoclonal immunoglobulins as assessed by IFE; a corresponding reduction of NT-proBNP levels was also observed (p<0.001). Survival was superior in responders than in non-responders (p<0.001). This finding was supported by a subsequent study by Kastritis et al. , which confirmed by multivariate analysis that a cardiac response was associated with a haematological response (46% vs. 0% in non-haematological responders; p<0.001).
Further studies have demonstrated a direct cardiotoxic effect of amyloidogenic FLCs , and support the clinical observation that a reduction in circulating monoclonal FLCs translates into a rapid improvement in cardiac function. Therefore, it is important to reduce the concentrations of cardiotoxic FLCs promptly in AL patients with cardiomyopathy.
28.7.2. sFLC response and renal outcome
Pinney et al.  assessed the value of the sFLC response in predicting long-term renal outcome in 923 patients with renal AL amyloidosis. Patients who achieved a greater sFLC response after chemotherapy demonstrated prolonged survival and superior renal outcomes. Patients who achieved more than a 90% FLC response at 6 months had an almost four-fold increase in the chance of renal response (p<0.001) and a lower rate of renal progression (p<0.001) compared with those achieving a FLC response of 0 - 50%. Among 752 patients with a baseline estimated glomerular filtration rate (eGFR) of ≥15 mL/min, those who achieved a 50 to 90% reduction or more than a 90% reduction in dFLC were less likely to experience renal progression requiring dialysis than patients achieving a <50% reduction in dFLC.
Rezk et al.  studied the prognostic value of the response to chemotherapy among 78 patients with AL amyloidosis who presented with advanced CKD (eGFR <20 mL/min/1.73m2). The median time to a composite end point of either death or dialysis was 17.3 months for patients who achieved a dFLC response of ≥90% at 3 months, compared to 5.3 months among patients who achieved a lesser response (p=0.001). The dFLC response remained prognostic in the subset of 45 patients who had renal amyloidosis without cardiac involvement (time to dialysis was 23.0 months compared to 6.2 months, p<0.007). The authors concluded that patients with advanced CKD due to renal AL amyloidosis should be treated urgently with the aim of achieving a rapid and deep clonal response, as this is associated with delayed dialysis and prolonged survival.
It should be noted that in cases of renal insufficiency, use of a modified renal reference interval for the κ/λ sFLC ratio may be appropriate. Application of this reference interval has been demonstrated to improve the diagnostic specificity of the sFLC ratio without affecting diagnostic sensitivity in patients with renal impairment (Section 6.3).