Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group

Wechalekar, Ashutosh; Cibeira, María Teresa; Gibbs, Simon; Jaccard, Arnaud; Kumar, Shaji; Merlini, Giampaolo; Palladini, Giovanni; Sanchorawala, Vaishali; Schönland, Stefan; Venner, Christopher P.; Boccadoro, Mario; Kastritis, Efstathios

doi:10.1080/13506129.2022.2093635

Cited by 53 publications

(45 citation statements)

References 105 publications

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“…A correct diagnosis, including the amyloid type, is required for proper treatment. Treatment options for the different variants have emerged rapidly during the last years (47,48), and the demands for an accurate diagnosis have significantly increased. The clinical diagnosis of amyloidosis is still based on tissue biopsy.…”

Section: Discussionmentioning

confidence: 99%

Tissue-based diagnosis of systemic amyloidosis: Experience of the informal diagnostic center at Uppsala University Hospital

Vesterlund

Ihse

Thelander

et al. 2022

ujms

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Diagnosis of systemic amyloidosis is a clinical challenge and usually relies on a tissue biopsy. We have developed diagnostic methods based on the presence of amyloid deposits in abdominal subcutaneous fat tissue. This tissue is also used to determine the biochemical type of amyloidosis, performed by western blot and immunohistochemical analyses with the aid of in-house developed rabbit antisera and mouse monoclonal antibodies. Mass spectrometric methods are under development for selected cases. The diagnostic outcome for 2018-2020 was studied. During this period, we obtained 1,562 biopsies, of which 1,397 were unfixed subcutaneous fat tissue with varying degrees of suspicion of systemic amyloidosis. Of these, 440 contained amyloid deposits. The biochemical nature of the amyloid was determined by western blot analysis in 319 specimens and by immunohistochemistry in further 51 cases.

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Section: Discussionmentioning

confidence: 99%

Tissue-based diagnosis of systemic amyloidosis: Experience of the informal diagnostic center at Uppsala University Hospital

Vesterlund

Ihse

Thelander

et al. 2022

ujms

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“…The International Society of Amyloidosis (ISA) and European Hematology Association (EHA) recently issued guidelines for the treatment of AL amyloidosis (Figure 1). 16,17 These guidelines are a first attempt to tailor treatment based on disease stage, age, and comorbidities, in light of the results of recent randomized trials. The first step is assessing eligibility to autologous stem cell transplant (ASCT).…”

Section: Selection Of Up-front Therapymentioning

confidence: 99%

“…16 Patients who are not eligible for ASCT should first be assessed for potential contraindication to bortezomib. 17 The most common contraindication is peripheral neuropathy, which is present in approximately 15% of patients, 1 but pulmonary fibrosis should also be considered. In the absence of contraindications to bortezomib, the treatment choice should be based on cardiac staging according to the European modification of the Mayo 2004 staging system.…”

Section: Selection Of Up-front Therapymentioning

confidence: 99%

Individualized Approach to Management of Light Chain Amyloidosis

Palladini

Milani

2023

Journal of the National Comprehensive Cancer Network

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Systemic light chain (AL) amyloidosis is caused by a B-cell (most commonly plasma cell) clone that produces a toxic light chain that forms amyloid fibrils in tissues and causes severe, progressive organ dysfunction. The clinical presentation is protean, and patients are usually extremely frail, thus requiring careful adaptation of the treatment approach. However, the severity of organ involvement can be accurately assessed with biomarkers that allow a sharp prognostic stratification and precise tailoring of the treatment strategy. Moreover, the availability of biomarker-based response criteria also allows adjustment of the treatment approach over time. The recent completion of 3 large randomized clinical trials has offered new evidence for designing appropriate treatments. All this information has recently been integrated in the joint guidelines of the International Society of Amyloidosis and the European Hematology Association for the treatment of AL amyloidosis. Other clinical trials are underway testing new agents directed against the amyloid clone and the amyloid deposits. Our understanding of the peculiarities of the amyloid clone, as well as our ability to detect residual clonal disease and improve organ dysfunction, are also being refined and will result in more precise personalization of the treatment approach.

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“…The main options are autologous stem cell transplant (ASCT) or anti-PCD chemotherapy/immunotherapy to eliminate the underlying PCD ( 21 , 22 ). However, very few patients are candidates for ASCT as strict eligibility criteria, including age < 70 years, low troponin and natriuretic peptides values, preserved cardiac, hepatic and renal function, are essential to reduce transplant-related mortality ( 22 – 27 ). Many patients eligible for ASCT benefit from induction therapy with anti-PCD regimens to prepare them for transplant and to improve outcomes ( 23 , 25 , 28 ).…”

Section: Standard Of Care and Limitationsmentioning

confidence: 99%

“…For patients who are ineligible for ASCT, and those who decline the procedure, anti-PCD chemotherapy is the only option ( 23 , 28 ). Current guidelines recommend a combination of cyclophosphamide, bortezomib, dexamethasone (CyBorD), and daratumumab as first-line therapy for newly diagnosed patients with AL amyloidosis ( 27 , 28 ). Cyclophosphamide is an alkylating agent that causes damage to DNA strands resulting in apoptosis of the cell ( 30 ).…”

Section: Standard Of Care and Limitationsmentioning

confidence: 99%

Changing paradigm in the treatment of amyloidosis: From disease-modifying drugs to anti-fibril therapy

Quarta

Fontana

Damy

et al. 2022

Front. Cardiovasc. Med.

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Cardiac amyloidosis is a rare, debilitating, and usually fatal disease increasingly recognized in clinical practice despite patients presenting with non-specific symptoms of cardiomyopathy. The current standard of care (SoC) focuses on preventing further amyloid formation and deposition, either with anti-plasma cell dyscrasia (anti-PCD) therapies in light-chain (AL) amyloidosis or stabilizers of transthyretin (TTR) in transthyretin amyloidosis (ATTR). The SoC is supplemented by therapies to treat the complications arising from organ dysfunction; for example, heart failure, arrhythmia, and proteinuria. Advancements in treatments have improved patient survival, especially for those whose disease is detected and for whom treatment is initiated at an early stage. However, there still are many unmet medical needs, particularly for patients with severe disease for whom morbidity and mortality remain high. There currently are no approved treatments to reverse amyloid infiltration and deplete the amyloid fibrils already deposited in organs, which can continue to cause progressive dysfunction. Anti-fibril therapies aimed at removing the deposited fibrils are being investigated for safety and efficacy in improving outcomes for patients with severe disease. However, there is no clinical evidence yet that removing deposited amyloid fibrils will improve organ function, thereby improving quality of life or extending life. Nevertheless, anti-fibril therapies are actively being investigated in clinical trials to evaluate their ability to complement and synergize with current SoC.

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Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group

Cited by 53 publications

References 105 publications

Tissue-based diagnosis of systemic amyloidosis: Experience of the informal diagnostic center at Uppsala University Hospital

Tissue-based diagnosis of systemic amyloidosis: Experience of the informal diagnostic center at Uppsala University Hospital

Individualized Approach to Management of Light Chain Amyloidosis

Changing paradigm in the treatment of amyloidosis: From disease-modifying drugs to anti-fibril therapy

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