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. 2025 Sep 11:S1936-878X(25)00450-4.
doi: 10.1016/j.jcmg.2025.07.017. Online ahead of print.

Changes in Myocardial Light Chain Amyloid Burden After Plasma Cell Therapy

Dominik C Benz  1 , Olivier F Clerc  1 , Sarah A M Cuddy  2 , Vasvi Singh  2 , Marie Foley Kijewski  3 , Giada Bianchi  4 , Andrew J Yee  5 , Frederick L Ruberg  6 , Michael Jerosch-Herold  7 , Raymond Y Kwong  7 , Marcelo F Di Carli  3 , Ronglih Liao  8 , Rodney H Falk  9 , Sharmila Dorbala  10
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Changes in Myocardial Light Chain Amyloid Burden After Plasma Cell Therapy

Dominik C Benz et al. JACC Cardiovasc Imaging. .

Abstract

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).

Keywords: AL amyloidosis; CMR; PET/CT; amyloid PET; cardiac; florbetapir; treatment response.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by grants from the National Institutes of Health and the American Heart Association (Dr Dorbala: R01 HL 130563, K24 HL 157648, AHA16 CSA 2888 0004, AHA19SRG34950011; Dr Falk: R01 HL 130563; Dr Liao: AHA16 CSA 2888 0004, AHA19SRG34950011). Dr Benz has received a research development grant from the Swiss National Science Foundation (grant P400PM_199305) and from the Advanced Clinician Scientist Program of University Medicine Zurich UMZH, investigator-initiated research funding from AstraZeneca, and consulting fees from Pfizer and AstraZeneca. Dr Clerc has received research funding from the International Society of Amyloidosis and Pfizer. Dr Cuddy has received investigator-initiated research funding from Pfizer; and consulting fees from Ionis Pharmaceuticals, AstraZeneca, BridgeBio, and Novo Nordisk. Dr Dorbala has received investigator-initiated funding from Pfizer, GE HealthCare, Attralus, and Siemens; and consulting fees from Pfizer and GE HealthCare. Dr Falk has received investigator-initiated research funding from GlaxoSmithKline and Akcea; and consulting fees from Ionis Pharmaceuticals, Alnylam Pharmaceuticals, and Caelum Biosciences. Dr Ruberg has received investigator-initiated research funding from Pfizer, Anumana, and AstraZeneca; and consulting fees from Attralus and AstraZeneca. Dr Yee has received consulting fees from AbbVie, Adaptive Biotechnologies, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, Regeneron, Sanofi, Sebia, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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