Changes in Myocardial Light Chain Amyloid Burden After Plasma Cell Therapy.

BACKGROUND Current therapies for light chain (AL) amyloidosis target the plasma cell dyscrasia, but their effect on myocardial amyloid fibril burden remains poorly defined. OBJECTIVES The authors aimed to assess longitudinal changes in myocardial amyloid burden after plasma cell-directed chemotherapy. METHODS This prospective study included 81 patients (58 with AL amyloid cardiomyopathy and 23 with AL amyloidosis without cardiomyopathy) with recently diagnosed, biopsy-proven AL amyloidosis, who underwent serial 18F-florbetapir positron emission tomography/computed tomography and cardiac magnetic resonance (including extracellular volume [ECV]) at baseline, 6 months (n = 52), and/or 12 months (n = 37). Molecular amyloid burden was estimated as 18F-florbetapir percentage injected dose (%ID), and changes are presented as absolute and relative %ID changes. Cardiac biomarker response was defined as a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) >30% and >300 ng/L when baseline NT-proBNP ≥650 ng/L. All change comparisons were paired within patients. RESULTS In AL amyloid cardiomyopathy, amyloid burden decreased significantly at 6 and 12 months after therapy initiation (median absolute [relative] change %ID: -0.3% [-13%]; P = 0.002; and -0.3% [15%]; P = 0.003). Changes in %ID correlated moderately with changes in NT-proBNP at 12 months (ρ = 0.531). Of note, %ID decreased significantly among biomarker responders (P < 0.001), whereas there was no change in nonresponders (P = 0.542). In contrast, ECV did not change in biomarker responders (P = 0.193) or nonresponders (P = 0.695). In AL amyloidosis without cardiomyopathy, %ID did not change (P = 0.523), whereas ECV increased (P = 0.011). CONCLUSIONS Myocardial AL amyloid burden estimated by 18F-florbetapir %ID decreases in participants undergoing plasma cell therapy and is detectable at 6 months. Molecular amyloid and ECV changes probably reflect distinct aspects of myocardial remodeling in AL amyloidosis. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]: NCT02641145).