Rapid Complete Response to Single-Agent Bcl-2 Inhibitor Venetoclax in a Heart-Transplanted Patient with Triple Refractory Immunoglobulin Light-Chain Amyloidosis

2020 ◽  
Vol 143 (5) ◽  
pp. 500-503 ◽  
Author(s):  
Charlotte Gran ◽  
Johanna Borg Bruchfeld ◽  
Fredrik Ellin ◽  
Hareth Nahi
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Treatment Options ◽  
Single Agent ◽  
Complete Response ◽  
Organ Damage ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Cytogenetic Aberration ◽  
Immunoglobulin Light Chain Amyloidosis

Immunoglobulin light-chain amyloidosis (AL) is a disease with limited treatment options due to the frailty of patients caused by organ damage. Since the clonal plasma cells often contain the cytogenetic aberration t(11;14), the Bcl-2 inhibitor venetoclax is suggested to have a role in the treatment of AL. Here, we report of a heart-transplanted patient, refractory to multiple therapies, reaching a rapid complete response with single-agent venetoclax.

scholarly journals Beyond the plasma cell: emerging therapies for immunoglobulin light chain amyloidosis

Blood ◽  
2016 ◽  
Vol 127 (19) ◽  
pp. 2275-2280 ◽  
Author(s):  
Brendan M. Weiss ◽  
Sandy W. Wong ◽  
Raymond L. Comenzo
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Organ Damage ◽  
Immunoglobulin Light Chain ◽  
Organ Function ◽  
Fatal Disease ◽  
Mortality And Morbidity ◽  
Amyloid Deposits ◽  
Emerging Therapies ◽  
Immunoglobulin Light Chain Amyloidosis

Abstract Systemic immunoglobulin light chain (LC) amyloidosis (AL) is a potentially fatal disease caused by immunoglobulin LC produced by clonal plasma cells. These LC form both toxic oligomers and amyloid deposits disrupting vital organ function. Despite reduction of LC by chemotherapy, the restoration of organ function is highly variable and often incomplete. Organ damage remains the major source of mortality and morbidity in AL. This review focuses on the challenges posed by emerging therapies that may limit the toxicity of LC and improve organ function by accelerating the resorption of amyloid deposits.

scholarly journals Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy

2016 ◽  
Vol 135 (3) ◽  
pp. 172-190 ◽  
Author(s):  
Eli Muchtar ◽  
Francis K. Buadi ◽  
Angela Dispenzieri ◽  
Morie A. Gertz
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Treatment Options ◽  
Organ Damage ◽  
Major Effect ◽  
Response To Treatment ◽  
Al Amyloidosis ◽  
Prognostic Effect ◽  
Amyloid Light Chain ◽  
Immunoglobulin Light Chain Amyloidosis

Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.

Nonchemotherapy Treatment of Immunoglobulin Light Chain Amyloidosis

2020 ◽  
Vol 143 (4) ◽  
pp. 373-380
Author(s):  
Layla Van Doren ◽  
Suzanne Lentzsch
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Cell Clone ◽  
Standard Of Care ◽  
Organ Damage ◽  
Current Therapy ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis

Immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare, life-threatening disease characterized by the deposition of misfolded proteins in vital organs such as the heart, the lungs, the kidneys, the peripheral nervous system, and the gastrointestinal tract. This causes a direct toxic effect, eventually leading to organ failure. The underlying B-cell lymphoproliferative disorder is almost always a clonal plasma cell disorder, most often a small plasma cell clone of <10%. Current therapy is directed toward elimination of the plasma cell clone with the goal of preventing further organ damage and reversal of the existing organ damage. Autologous stem cell transplantation has been shown to be a very effective treatment in patients with AL amyloidosis, although it cannot be widely applied as patients are often frail at presentation, making them ineligible for transplantation. Treatment with cyclophosphamide, bortezomib, and dexamethasone has emerged as the standard of care for the treatment of AL amyloidosis. Novel anti-plasma cell therapies, such as second generation proteasome inhibitors, immunomodulators, monoclonal antibodies targeting a surface protein on the plasma cell (daratumumab, elotuzumab), and the small molecular inhibitor venetoclax, have continued to emerge and are being evaluated in combination with the standard of care. However, there is still a need for therapies that directly target the amyloid fibrils and reverse organ damage. In this review, we will discuss current and emerging nonchemotherapy treatments of AL amyloidosis, including antifibril directed therapies under current investigation.

scholarly journals Systemic Light Chain Amyloidosis (Congo Red Inconclusive) with Underlyng Clonal Expansion Not Meeting the Criteria of Light Chain Monoclonal Gammopathy of Renal Significance or Light Chain Myeloma:A Case Report

2020 ◽  
Vol 07 (04) ◽  
pp. 15-19
Author(s):  
Sanjay Kumar ◽  
Keyword(s):  
Light Chain ◽  
Congo Red ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Clonal Expansion ◽  
Chronic Diarrhoea ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis

Fifty-eight-year-old male admitted for evaluation of nephrotic syndrome and chronic diarrhoea was detected to have Immunoglobulin light chain amyloidosis (AL Amyloidosis) which was congo red inconclusive from renal biopsy. Bone marrow biopsy showed monoclonal plasma cells of 40% and light chain assay showed predominance of immunoglobulin lambda light chain. The diagnosis was neither fitting into the current diagnostic criteria for light chain Monoclonal Gammopathy of Renal Significance (MGRS) nor light chain myeloma. Literature is scarce regarding patients with AL amyloidosis having underlying clonal expansion not meeting the criteria of light chain myeloma or light chain MGRS.

scholarly journals Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Linchun Xu ◽  
Yongzhong Su
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Amyloid Fibril ◽  
Treatment Modalities ◽  
Driver Gene ◽  
Immunoglobulin Light Chain ◽  
Disease Evolution ◽  
Genetic Aberrations ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis

AbstractImmunoglobulin light chain amyloidosis (AL) is an indolent plasma cell disorder characterized by free immunoglobulin light chain (FLC) misfolding and amyloid fibril deposition. The cytogenetic pattern of AL shows profound similarity with that of other plasma cell disorders but harbors distinct features. AL can be classified into two primary subtypes: non-hyperdiploidy and hyperdiploidy. Non-hyperdiploidy usually involves immunoglobulin heavy chain translocations, and t(11;14) is the hallmark of this disease. T(11;14) is associated with low plasma cell count but high FLC level and displays distinct response outcomes to different treatment modalities. Hyperdiploidy is associated with plasmacytosis and subclone formation, and it generally confers a neutral or inferior prognostic outcome. Other chromosome abnormalities and driver gene mutations are considered as secondary cytogenetic aberrations that occur during disease evolution. These genetic aberrations contribute to the proliferation of plasma cells, which secrete excess FLC for amyloid deposition. Other genetic factors, such as specific usage of immunoglobulin light chain germline genes and light chain somatic mutations, also play an essential role in amyloid fibril deposition in AL. This paper will propose a framework of AL classification based on genetic aberrations and discuss the amyloid formation of AL from a genetic aspect.

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