Clinical presentation and outcomes in light chain amyloidosis patients with non-evaluable serum free light chains

Abstract

Hematologic response criteria in light chain (AL) amyloidosis require the difference in involved and uninvolved free light chains (dFLC) to be at least 5 mg/dl. We describe the clinical presentation and outcomes of newly diagnosed amyloidosis patients with dFLC <5 mg/dl (non-evaluable dFLC; 14%, n=165) compared with patients with dFLC ⩾5 mg/dl (evaluable dFLC; 86%, n=975). Patients with non-evaluable dFLC had less cardiac involvement (40% vs 80%, P<0.001), less liver involvement (11% vs 17%, P=0.04) and a trend toward less gastrointestinal involvement (18% vs 25%, P=0.08). However, significantly higher renal involvement (72% vs 56%, P=0.0002) was observed in the non-evaluable dFLC cohort. Differences in treatment patterns were observed, with 51% of treated patients undergoing upfront stem cell transplantation in the non-evaluable cohort compared with 28% in the evaluable dFLC group (P<0.001). Progression-free survival (61 vs 13 months, P<0.001) and overall survival (OS; 101 vs 29 months, P<0.001) were significantly longer in the non-evaluable dFLC cohort. Normalization of involved light chain levels and decrease in dFLC <1 mg/dl (baseline at least 2 mg/dl) were predictive of OS and associated with better dialysis-free survival and may be used for response assessment in patients with non-evaluable FLC levels.

Systemic immunoglobulin light chain amyloidosis

“…Patients with AL amyloidosis and a bone marrow plasma cell infiltrate of >10% have poorer survival that is comparable to patients with concomitant overt multiple myeloma 73 . Individuals with a very low (<50 mg/L) dFLC level have a significantly better outcome irrespective of cardiac stage [74][75][76] . The Mayo Clinic group incorporated the dFLC level (with a cutoff value of 180 mg/L) in their revised staging system ( Figure 6B) 77,78 .…”

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] .…”

Impact of minimal residual negativity using next generation flow cytometry on outcomes in light chain amyloidosis

“…Light chain (AL) amyloidosis is typically associated with a low clonal plasma cell burden . However, even low levels of unstable light chains secreted by these plasma cells can deposit in organs like heart, kidney, liver and nerves, resulting in organ dysfunction . A rapid reduction of light chains to very low levels with treatment results in organ improvement and better survival .…”