Response assessment in AL amyloidosis
| Hematologic response . | CR . | VGPR . | PR . | PD . |
|---|---|---|---|---|
| Serum protein electrophoresis/immunofixation | Serum negative for monoclonal proteins by immunofixation | ≥50% reduction in current serum monoclonal protein levels >0.5 g/dL | If progressing from CR, any detectable monoclonal protein If progressive from PR or SD, ≥50% increase in the serum M protein to >0.5 g/dL | |
| Urine protein electrophoresis/immunofixation | Urine negative for monoclonal proteins by immunofixation | ≥50% reduction in current urine M protein levels >100 mg/d with a visible peak | If progressive from PR or SD, ≥50% increase in urine M protein to >200 mg/d with visible peak present | |
| Serum free light chains | Normal serum free light chain ratio or the uninvolved serum free light chain concentration is greater than the involved serum free light chain concentration with or without an abnormal free light chain ratio | Reduction in the difference between the involved and uninvolved serum free light chain to <40 mg/L | ≥50% reduction in current free light chain levels >10 mg/dL | Serum free light chain increase of ≥50% to >10 mg/dL (100 mg/L) |
| Organ response | Response | Stable disease | PD | |
| Cardiac | Requires any of the following: ≥2-mm decrease in mean intraventricular septal wall thickness by echocardiogram ≥20% increase in LVEF ≥2 grade decrease in New York Heart Association functional class without an increase in diuretic use and no increase in wall thickness Reduction (≥30% and ≥300 ng/L) of NT-proBNP in patients whom the eGFR is ≥45 mL/min/1.73 m2 | Does not meet the criteria for cardiac response or progressive disease | Requires any of the following: ≥2-mm increase from baseline in the intraventricular wall thickness by echocardiogram ≥10% decrease in the LVEF ≥1 grade increase in New York Heart Association functional class | |
| Renal | ≥50% decrease of at least 0.5 g/d (500 mg/24 h) in 24-h urine protein of >0.5 g/d (500 mg/24 h) pretreatment and Creatinine clearance or serum creatinine must not have worsened by ≥25% over baseline | Does not meet the criteria for renal response or progressive disease | Requires any of the following: ≥50% increase of at least 1 g/d (1000 mg/24 h) for urine protein to >1 g/d (1000 mg/24 h) 25% worsening of serum creatinine or creatinine clearance | |
| Hepatic | Requires all of the following: ≥2-cm decrease in liver span if hepatomegaly present (liver >15 cm) ≥50% decrease and/or normalization of serum ALP level | Does not meet the criteria for hepatic response or progressive disease | Requires the following: ≥50% increase in the serum ALP level | |
| Autonomic nervous system | Resolution of symptomatic orthostatic hypotension | Does not meet the criteria for autonomic neuropathy response or progressive disease | Worsening of symptomatic orthostatic hypotension | |
| Peripheral nervous system | Requires any of the following: Resolution of abnormal physical findings Resolution or improvement of abnormal EMG and/or NCV findings | Does not meet the criteria for peripheral neuropathy response or progressive disease | Requires any of the following: Worsening of physical findings Worsening of EMG and/or NCV findings |
| Hematologic response . | CR . | VGPR . | PR . | PD . |
|---|---|---|---|---|
| Serum protein electrophoresis/immunofixation | Serum negative for monoclonal proteins by immunofixation | ≥50% reduction in current serum monoclonal protein levels >0.5 g/dL | If progressing from CR, any detectable monoclonal protein If progressive from PR or SD, ≥50% increase in the serum M protein to >0.5 g/dL | |
| Urine protein electrophoresis/immunofixation | Urine negative for monoclonal proteins by immunofixation | ≥50% reduction in current urine M protein levels >100 mg/d with a visible peak | If progressive from PR or SD, ≥50% increase in urine M protein to >200 mg/d with visible peak present | |
| Serum free light chains | Normal serum free light chain ratio or the uninvolved serum free light chain concentration is greater than the involved serum free light chain concentration with or without an abnormal free light chain ratio | Reduction in the difference between the involved and uninvolved serum free light chain to <40 mg/L | ≥50% reduction in current free light chain levels >10 mg/dL | Serum free light chain increase of ≥50% to >10 mg/dL (100 mg/L) |
| Organ response | Response | Stable disease | PD | |
| Cardiac | Requires any of the following: ≥2-mm decrease in mean intraventricular septal wall thickness by echocardiogram ≥20% increase in LVEF ≥2 grade decrease in New York Heart Association functional class without an increase in diuretic use and no increase in wall thickness Reduction (≥30% and ≥300 ng/L) of NT-proBNP in patients whom the eGFR is ≥45 mL/min/1.73 m2 | Does not meet the criteria for cardiac response or progressive disease | Requires any of the following: ≥2-mm increase from baseline in the intraventricular wall thickness by echocardiogram ≥10% decrease in the LVEF ≥1 grade increase in New York Heart Association functional class | |
| Renal | ≥50% decrease of at least 0.5 g/d (500 mg/24 h) in 24-h urine protein of >0.5 g/d (500 mg/24 h) pretreatment and Creatinine clearance or serum creatinine must not have worsened by ≥25% over baseline | Does not meet the criteria for renal response or progressive disease | Requires any of the following: ≥50% increase of at least 1 g/d (1000 mg/24 h) for urine protein to >1 g/d (1000 mg/24 h) 25% worsening of serum creatinine or creatinine clearance | |
| Hepatic | Requires all of the following: ≥2-cm decrease in liver span if hepatomegaly present (liver >15 cm) ≥50% decrease and/or normalization of serum ALP level | Does not meet the criteria for hepatic response or progressive disease | Requires the following: ≥50% increase in the serum ALP level | |
| Autonomic nervous system | Resolution of symptomatic orthostatic hypotension | Does not meet the criteria for autonomic neuropathy response or progressive disease | Worsening of symptomatic orthostatic hypotension | |
| Peripheral nervous system | Requires any of the following: Resolution of abnormal physical findings Resolution or improvement of abnormal EMG and/or NCV findings | Does not meet the criteria for peripheral neuropathy response or progressive disease | Requires any of the following: Worsening of physical findings Worsening of EMG and/or NCV findings |
Palladini et al. (2012)11 and Gertz et al. (2005).12
ALP, alkaline phosphatase; eGFR, estimated glomerular filtration rate; EMG, electromyography; NCV, nerve conduction velocity; PD, progressive disease; PR, partial response; SD, stable disease.