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. 2024 Nov 1;9(11):982-989.
doi: 10.1001/jamacardio.2024.2555.

Redefining Cardiac Involvement and Targets of Treatment in Systemic Immunoglobulin AL Amyloidosis

Aldostefano Porcari  1   2   3 , Ambra Masi  1 , Ana Martinez-Naharro  1 , Yousuf Razvi  1 , Rishi Patel  1 , Adam Ioannou  1 , Muhammad U Rauf  1 , Giulio Sinigiani  4 , Brendan Wisniowski  1 , Stefano Filisetti  5   6 , Jasmine Currie-Cathey  1 , Sophie O'Beara  1 , Tushar Kotecha  1 , Dan Knight  1 , James C Moon  7   8 , Gianfranco Sinagra  2   3 , Ruta Virsinskaite  1 , Janet Gilbertson  1 , Lucia Venneri  1 , Aviva Petrie  1 , Helen Lachmann  1 , Carol Whelan  1 , Peter Kellman  9 , Sriram Ravichandran  1 , Oliver Cohen  1 , Shameem Mahmood  1 , Charlotte Manisty  10 , Philip N Hawkins  1 , Julian D Gillmore  1 , Ashutosh D Wechalekar  1 , Marianna Fontana  1
Affiliations

Redefining Cardiac Involvement and Targets of Treatment in Systemic Immunoglobulin AL Amyloidosis

Aldostefano Porcari et al. JAMA Cardiol. .

Abstract

Importance: Cardiac amyloid infiltration is the key determinant of survival in systemic light-chain (AL) amyloidosis. Current guidelines recommend early switching therapy in patients with a nonoptimal or suboptimal response regardless of the extent of cardiac amyloid infiltration.

Objective: To assess the differences between serum biomarkers, echocardiography, and cardiovascular magnetic resonance (CMR) with extracellular volume (ECV) mapping in characterizing cardiac amyloid, the independent prognostic role of these approaches, and the role of ECV mapping to guide treatment strategies.

Design, setting, and participants: Consecutive patients newly diagnosed with systemic AL amyloidosis (2015-2021) underwent echocardiography, cardiac biomarkers, and CMR with ECV mapping at diagnosis. Data were analyzed from January to June 2024.

Main outcomes and measures: The primary outcomes of the study were all-cause mortality and hematological response as defined according to validated criteria: no response (NR), partial response (PR), very good partial response (VGPR), and complete response (CR). Secondary outcomes were the depth and speed of hematological response and overall survival according to ECV.

Results: Of 560 patients with AL amyloidosis, the median (IQR) age was 68 years (59-74 years); 346 patients were male (61.8%) and 214 female (38.2%). Over a median (IQR) 40.5 months 9-58 months), ECV was independently associated with mortality. In the landmark analysis at 1 month, long-term survival was independent of the achieved hematological response in ECV less than 0.30% and ECV of 0.31% to 0.40%, while it was dependent on the depth of the hematological response in ECV greater than 0.40%. In the landmark analysis at 6 months, survival was independent of the achieved hematological response in ECV less than 0.30% and dependent on achieving at least PR in ECV of 0.31% to 0.40%. Survival was dependent on achieving CR in ECV of 0.41% to 0.50% and ECV greater than 0.50%. Achieving a deep hematological response at 1 month was associated with better survival compared with 6 months in patients with ECV greater than 0.40% but not with ECV less than 0.40%.

Conclusions and relevance: This study found that ECV mapping, in systemic AL amyloidosis, is an independent predictor of prognosis, can help define the hematological response associated with better long-term outcomes for each patient and potentially inform treatment strategies.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kotecha reported speaking fees from Janssen outside the submitted work. Dr Knight reported grants from the British Heart Foundation (FS/CRLF/20/23004) and speaker honoraria and advisory board fees from Janssen Pharmaceuticals outside the submitted work. Dr Manisty reported speaking fees from Pfizer and being a co-founder of MycardiumAI outside the submitted work. Dr Hawkins reported consulting income from Alnylam. Dr Gillmore reported consultancy for Alexion, Alnylam, AstraZeneca, Attralus, Bridgebio, Eidos, Intellia, Ionis, Lycia, and Pfizer. Dr Wechalekar reported consulting income from Alexia, AstraZeneca, Janssen, Attralus, and Prothena. Dr Fontana reported support from a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/21/33447); consultancy and/or advisory board fees for Akcea, Alnylam, Alexion, AstraZeneca, Bridgebio/Eidos, Prothena, Attralus, Intellia, Ionis, Cardior, Janssen, Lexeo, Novo Nordisk, and Pfizer outside the submitted work; and research grants from Alnylam, Bridgebio, AstraZeneca, and Pfizer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association of Early Response (at 1 Month) and Survival Stratified by Baseline Extracellular Volume
Kaplan-Meier analysis of 60-month survival for patients with AL amyloidosis according to hematological response at 1 month. P values for intergroup comparison are shown only for subgroups with global P < .05. CR indicates complete response; NR, no response; PR, partial response; VGPR, very good partial response.
Figure 2.
Figure 2.. Association of Early Deep Hematological Response (Very Good Partial Response or Better [≥VGPR] at 1 Month) vs Late Deep Hematological Response (≥VGPR at 6 Months) and Overall Survival Stratified by Baseline Extracellular Volume
Kaplan-Meier analysis of 60-month survival for patients with AL amyloidosis according to time to a hematological response ≥VGPR. P values for intergroup comparison are shown only for subgroups with global P < .05.
See this image and copyright information in PMC

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