Patients with light-chain amyloidosis and low free light-chain burden have distinct clinical features and outcome

Abstract

The validated criteria of hematologic response in light-chain (AL) amyloidosis are based on the measurement of circulating free light chains (FLCs). Patients with a difference between involved and uninvolved FLC (dFLC) <50 mg/L cannot be assessed for response and are excluded from clinical trials. We compared the clinical characteristics and outcome of 203 newly diagnosed patients with dFLC <50 mg/L (low dFLC) with 866 patients with measurable dFLC (high dFLC) evaluated between 2004 and 2015. Heart involvement was significantly less common and less advanced in the low-dFLC group (43% vs 83% and Mayo stage III 45% vs 15%, both < .001), whereas renal involvement was more frequent (77% vs 63%, < .001) and more severe (renal stage III 26% vs 18%, = .001). Overall survival (OS) was significantly better in the low-dFLC group (median 117 vs 21 months, < .001), whereas no difference was seen in renal survival (RS). Within each Mayo stage, patients with low dFLC had a longer survival. In the low-dFLC group, complete response was associated with a significant advantage in OS (median not reached vs 117 months, = .005) and with a better RS. A reduction in dFLC after therapy of<10 mg/L was associated with a better OS and RS in patients with at least a dFLC >20 mg/L baseline. Nineteen percent of newly diagnosed patients with AL amyloidosis have low dFLC and had a better outcome. Hematologic response assessed with adapted criteria predicts OS and RS in these patients, who can thus be assessed for response and included in clinical trials with appropriate stratification.

A validated composite organ and hematologic response model for early assessment of treatment outcomes in light chain amyloidosis

“…In evaluable patients, HR was assessed using validated criteria 16 . Patients who had difference in involved and uninvolved free light chains (dFLC) <5 mg/dL were assessed for response by criteria of complete response (CR) only, based on recent data [22][23][24] . Organ involvement and response were assessed by using existing criteria as described in supplementary data 16,[25][26][27] .…”

Clinical features, laboratory characteristics and outcomes of patients with renal versus cardiac light chain amyloidosis

“…Our findings are in line with prior reports from our group as well as others, which demonstrate that patients with very small light chain burden (dFLC <50 mg/l) or low light chain burden (dFLC <196 mg/l) are more likely to have renal involvement. (Kumar et al , ; Dittrich et al , ; Milani et al , ; Sidana et al , ) In another series of 77 systemic AL amyloid patients with renal involvement, Wong et al () observed median dFLC levels 127 mg/l, with 60% of patients in this series having co‐existing cardiac involvement. Similarly, Kastritis et al () described a series of 125 patients with renal involvement, of whom 42% had co‐existing cardiac involvement.…”

Primary treatment of light-chain amyloidosis with bortezomib, lenalidomide, and dexamethasone

“…Measurable FLCs (ie, a dFLC $50 mg/L) were present in 29 patients (85%); in 4 patients, baseline dFLC was .20 mg/L, and these patients were also evaluable for response. 37,38 In Table 1, the characteristics of the patients are depicted in more detail.…”