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Review
. 2023 Jul 5:10:1212983.
doi: 10.3389/fcvm.2023.1212983. eCollection 2023.

Cardiovascular toxicity from therapies for light chain amyloidosis

Paolo Morfino  1 , Alberto Aimo  1   2 , Vincenzo Castiglione  1   2 , Michela Chianca  1 , Giuseppe Vergaro  1   2 , Carlo Maria Cipolla  3 , Antonella Fedele  3 , Michele Emdin  1   2 , Iacopo Fabiani  1   2 , Daniela Cardinale  3
Affiliations
Review

Cardiovascular toxicity from therapies for light chain amyloidosis

Paolo Morfino et al. Front Cardiovasc Med. .

Abstract

Amyloid light-chain (AL) amyloidosis is a hematological disorder characterized by abnormal proliferation of a plasma cell clone producing monoclonal free light chains that misfold and aggregate into insoluble fibrils in various tissues. Cardiac involvement is a common feature leading to restrictive cardiomyopathy and poor prognosis. Current first-line treatments aim at achieving hematological response by targeting the plasma cell clones, and these have been adapted from multiple myeloma therapy. Patients with AL amyloidosis often exhibit multiorgan involvement, making them susceptible to cancer therapy-related cardiovascular toxicity. Managing AL amyloidosis is a complex issue that requires enhanced knowledge of the cardio-oncological implications of hematological treatments. Future research should focus on implementing and validating primary and secondary prevention strategies and understanding the biochemical basis of oncological therapy-related damage to mitigate cardiovascular toxicity.

Keywords: AL amyloidosis; cardiac amyloidosis; cardiovascular toxicity; chemotherapy; treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic of therapeutic targets and cardiovascular toxicity in light chain amyloidosis. The Figure summarizes the targets, mechanisms of action and cardiovascular toxicities of the most frequently used drugs in AL amyloidosis. PIs impair the function of the proteasome, inducing protein accumulation. IMiDs induce the proteasome-mediated degradation of IKZF transcription factors and exert both direct and indirect (through stimulation of immune response and anti-angiogenetic effect) cytotoxic effect. Daratumumab causes ADCC, CDC, and cellular apoptosis by targeting CD38 on plasma cells. Alkylating agents induce DNA damage, thus inhibiting cellular transcription and replication. ASCT consists of autologous bone marrow substitution, which represses the proliferation of abnormal plasma cell clones. ADCC, antibody-dependent cell cytotoxicity; AL, light chain amyloidosis; ASCT, autologous stem cell transplant; ATE, arterial thromboembolism; CDC, complement-dependent cytotoxicity; DM, diabetes mellitus; HF, heart failure; IMiD, immunomodulatory drug; MI, myocardial infarction; PD, pericardial disease; PH, pulmonary hypertension; PI, proteasome inhibitor; VTE, venous thromboembolism.
Figure 2
Figure 2
Clinical flow chart of cardio-oncological follow-up in patients with light chain amyloidosis. HDM/ASCT, high dose melphalan followed by autologous stem cell transplant; AL, light chain amyloidosis; BMD, bortezomib-melphalan-dexamethasone; BP, blood pressure; CyBorD, cyclophosphamide-bortezomib-dexamethasone; CV, cardiovascular, Dara, daratumumab; dex, dexamethasone; ECG, electrocardiogram; IMiD, immunomodulatory drug; NP, natriuretic peptide; PI, proteasome inhibitor; Tn, troponin; TTE, transthoracic echocardiogram.
See this image and copyright information in PMC

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