Systemic Amyloidosis Due to Clonal Plasma Cell Diseases

Bianchi, Giada; Kumar, Santosh

doi:10.1016/j.hoc.2020.08.001

Cited by 12 publications

(6 citation statements)

References 64 publications

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“…Immunoglobulin light chain (AL) amyloidosis arises from a plasma cell dyscrasia that results in the overproduction of nonfunctional immunoglobulins [ 1 ]. These misfolded proteins aggregate into insoluble β-pleated amyloid fibrils, commonly known as AL amyloids, which deposit within various organs.…”

Section: Introductionmentioning

confidence: 99%

Renal AL Amyloidosis: Updates on Diagnosis, Staging, and Management

Shafqat,

Elmaleh,

Mushtaq

et al. 2024

JCM

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AL amyloidosis is caused by the excessive production of nonfunctional immunoglobulins, leading to the formation of amyloid fibrils that damage vital organs, especially the heart and kidneys. AL amyloidosis presents with non-specific symptoms such as fatigue, weight loss, numbness, pain, and nephrotic syndrome. Consequently, diagnosis is often delayed, and patients typically present with advanced disease at diagnosis. The Pavia renal staging model stratifies patients based on their likelihood of progressing to dialysis. Treatment with daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (i.e., Dara-CyBorD) was effective in inducing renal response in the landmark phase III ANDROMEDA trial and reducing early mortality. However, determining the most appropriate treatment regimen for relapsed or refractory cases remains a challenge due to various patient- and disease-related factors. Encouragingly, t(11:14) may be a positive indicator of therapy responses to the anti-BCL2 therapy venetoclax. Moreover, it is increasingly possible—for the first time—to clear AL amyloid fibrils from peripheral organs by leveraging novel anti-fibril immunotherapeutic approaches, although these medications are still under investigation in clinical trials. Given these advancements, this review provides a comprehensive overview of the current strategies for diagnosing, staging, treating, and monitoring AL amyloidosis, emphasizing renal involvement.

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Section: Introductionmentioning

confidence: 99%

Renal AL Amyloidosis: Updates on Diagnosis, Staging, and Management

Shafqat,

Elmaleh,

Mushtaq

et al. 2024

JCM

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“…Immunoglobulin light chain (AL) amyloidosis is a rare monoclonal B-cell or plasma cell disorder characterized by the aggregation of misfolded monoclonal light chain kappa or lambda, which form insoluble amyloid fibrils with a beta-sheet structure[ 1 ] that are deposited and accumulated in nearly any organ or tissue[ 2 ]. Cardiac involvement is very frequent in AL amyloidosis (61% of patients) and can lead to heart failure because of infiltrative heart disease, which is the main prognostic factor and carries a poor prognosis[ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Pomolidomide for relapsed/refractory light chain amyloidosis after resistance to both bortezomib and daratumumab: A case report

Li¹,

Pan²,

Qiu³

et al. 2022

World J Clin Cases

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BACKGROUND Immunoglobulin light chain (AL) amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue, with cardiac involvement being very frequent (61%). Early diagnosis is of high importance because early initiation of treatment in AL amyloidosis may improve outcomes. Despite the administration of immunotherapeutic agents, in particular bortezomib and daratumumab, which have improved the outcomes of AL amyloidosis, anti-plasma cell therapy remains suboptimal for some patients. CASE SUMMARY We report the case of a 55-year-old man presenting with heart failure who was diagnosed with cardiac AL amyloidosis by an endomyocardial biopsy. He experienced a short-term hematological remission with no organ response after being administered a bortezomib-daratumumab containing regimen. The treatment was switched to pomolidomide due to pulmonary involvement and progressive pleural effusion, in which flow cytometry analysis showed abnormal plasma cells. After two cycles of this regimen, the pleural effusion was controlled effectively with no recurrence. CONCLUSION This case emphasizes the crucial role of endomyocardial biopsy in early diagnosis of cardiac amyloidosis and suggests that pomolidomide may be an effective treatment for patients with AL amyloidosis that is relapsed/refractory to both bortezomib and daratumumab.

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“…The shared fundamental pathogenetic mechanism of these conditions is the deposition in target organs of polymers of a misfolded protein, organized in fibrils, in association with chaperone proteins [2]. The amyloidogenic precursor protein defines the subtype of amyloidosis, determines the pattern of organ involvement and disease natural history, and ultimately dictates treatment approach [3]. In AL amyloidosis, the clonal Ig free light chain (FLC) is the precursor protein of amyloid fibrils.…”

Section: Introductionmentioning

confidence: 99%

Laboratory-Based Rationale for Targeting the Protein Homeostasis Network in AL Amyloidosis

Bianchi

Moscvin

Comenzo

2022

Hemato

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AL amyloidosis is an incurable plasma cell dyscrasia with limited therapeutic options. The pathogenetic mechanism in AL amyloidosis is the deposition of insoluble fibrillary aggregates of misfolded immunoglobulin (Ig) free light chains (FLC) and chaperone proteins in target organs. Therefore, AL amyloidosis is the prototypic, protein-toxicity hematologic disorder. Based on laboratory evidence of increased, constitutive proteotoxic stress, PCs are intrinsically vulnerable to agents that target proteins whose function is to guarantee that nascent polypeptides either reach a functional conformation or are disposed of (proteostasis network). The clinical efficacy of proteasome inhibitors (PIs), such as bortezomib, in the treatment of plasma cell (PC) disorders has provided proof of concept that disrupting protein homeostasis is an effective and generally safe therapeutic approach. Therefore, the intrinsic biology of PC offers us the opportunity to rationally develop therapies that target this distinct proteostasis vulnerability of PC dyscrasias. In this manuscript, we will review the laboratory rationale for the effectiveness of FDA-approved and investigational agents targeting protein homeostasis in AL amyloidosis and related PC disorders.

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Systemic Amyloidosis Due to Clonal Plasma Cell Diseases

Cited by 12 publications

References 64 publications

Renal AL Amyloidosis: Updates on Diagnosis, Staging, and Management

Renal AL Amyloidosis: Updates on Diagnosis, Staging, and Management

Pomolidomide for relapsed/refractory light chain amyloidosis after resistance to both bortezomib and daratumumab: A case report

Laboratory-Based Rationale for Targeting the Protein Homeostasis Network in AL Amyloidosis

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