EMN22

a.       Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in Congo Red stained tissue specimens (excluding bone marrow) or characteristic electron microscopy appearance

Considerations for specific populations where other types of amyloidosis may be encountered:

–           For male subjects over 70 years of age who have cardiac involvement only, and subjects of African descent (black subjects), mass spectrometry, immunoelectron microscopy, or other immunohistochemistry-based typing of AL amyloid in a tissue biopsy or a negative bone scintigraphy with Tc99-PYP or –DPD is recommended to rule out other types of amyloidosis such as age related amyloidosis and/or hereditary amyloidosis (ATTR mutation)

AND

b.       Measurable disease of amyloid light chain amyloidosis as defined by at least ONE of the following:

–           serum monoclonal protein ≥0.5 g/dL by protein electrophoresis (routine serum protein electrophoresis and immunofixation performed at local lab)

–           serum free light chain (FLC) ≥2.0 mg/dL (20 mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) ≥2mg/dL (20 mg/L). Serum FLCs will be measured using the Freelite assay at a central laboratory.

AND

c.       Cardiac involvement by AL amyloidosis according to consensus guidelines

a.         Absolute neutrophil count ≥1.0 × 10⁹/L;

b.         Hemoglobin level ≥10.0 g/dL (≥5 mmol/L)

c.          Platelet count ≥75 × 10⁹/L; platelet transfusions are NOT acceptable

d.         Alanine aminotransferase level (ALT) ≤2.5 x ULN;

e.         Aspartate aminotransferase (AST) ≤2.5 x ULN

f.           Total bilirubin level ≤1.5 × ULN, except for subjects with history of Gilbert Syndrome, in which case direct bilirubin ≤ 2 × ULN

g.         Estimated Glomerular Filtration Rate (eGFR) ≥20 mL/min; Please note that the eGFR is measured by using   the CKD-EPI equation