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Current Hematologic Malignancy Reports Jun 2020Light chain (AL) amyloidosis is an insidious progressive disease which results in significant morbidity and inevitable mortality if not diagnosed and treated promptly.... (Review)
Review
PURPOSE OF REVIEW
Light chain (AL) amyloidosis is an insidious progressive disease which results in significant morbidity and inevitable mortality if not diagnosed and treated promptly. This review will highlight recent developments and summarize critical clinical points and updated practice changes for the clinician in 2020.
RECENT FINDINGS
Comparative analyses of staging systems, updated prognostic tools, and treatment response criteria now allow for improved patient stratification and treatment decisions; the role of minimal residual disease in response assessment is still being assessed. Clinical and genetic predictors for long-term survivors have been highlighted. Standard-of-care front-line bortezomib and the integration of anti-CD38 monoclonal antibodies in the relapsed disease have transformed treatment approach in recent years. Various clinical trials in the pipeline include novel anti-plasma cell therapies and therapies directed against amyloid deposits which promise to further advance the treatment landscape. Diagnosis, response assessment, and treatment paradigms for AL amyloidosis have evolved significantly in the past 15 years, translating into superior outcomes and increased chances of long-term survival for AL amyloidosis.
Topics: ADP-ribosyl Cyclase 1; Animals; Antibodies, Monoclonal; Bortezomib; Clinical Decision-Making; Humans; Immunoglobulin Light-chain Amyloidosis; Immunologic Factors; Membrane Glycoproteins; Predictive Value of Tests; Proteasome Inhibitors; Risk Factors; Stem Cell Transplantation; Treatment Outcome
PubMed: 32394186
DOI: 10.1007/s11899-020-00574-5 -
European Journal of Haematology Nov 2023This study evaluated data from six Swedish national registries to fill current evidence gaps on the epidemiology, clinical burden, and overall survival (OS) associated...
OBJECTIVES
This study evaluated data from six Swedish national registries to fill current evidence gaps on the epidemiology, clinical burden, and overall survival (OS) associated with light-chain (AL) amyloidosis.
METHODS
Patients newly diagnosed with AL amyloidosis were identified using six linked Swedish nationwide population-based registers. For each case, individuals from the general population were selected and matched with a maximum ratio of 1:5 based on age, sex, calendar year, and county.
RESULTS
846 patients newly diagnosed with AL amyloidosis and 4227 demographically matched individuals were identified. From 2011 to 2019, annual AL amyloidosis incidence increased from 10.5 to 15.1 cases per million. At baseline, patients with AL amyloidosis had a significantly higher disease burden including higher rates of cardiac and renal failure relative to the comparison group. Among patients with AL amyloidosis, 21.5% had incident heart failure and 17.1% had incident renal failure after initial diagnosis. Median OS for patients with AL amyloidosis was 56 months versus not reached in the matched general population comparison group.
CONCLUSION
The incidence of newly diagnosed AL amyloidosis in Sweden increased over time with AL amyloidosis being associated with a higher risk of cardiac/renal failure and all-cause mortality compared with the general population.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Sweden; Amyloidosis; Heart Failure; Renal Insufficiency; Retrospective Studies
PubMed: 37533343
DOI: 10.1111/ejh.14063 -
Hematology. American Society of... Dec 2021Systemic light chain (AL) amyloidosis is a protein misfolding disorder characterized by the deposition of abnormal immunoglobulin light chains in fibrillary aggregates,... (Review)
Review
Systemic light chain (AL) amyloidosis is a protein misfolding disorder characterized by the deposition of abnormal immunoglobulin light chains in fibrillary aggregates, resulting in end-organ damage. Several unique challenges face treating physicians, including delayed diagnosis, advanced vital organ involvement, and morbidity with treatment. Aggressive supportive care and risk-adapted application of plasma cell-directed therapies are the cornerstones of management. The therapeutic revolution in multiple myeloma will likely further expand the arsenal against plasma cells. Careful investigation of these agents will be critical to establish their role in this fragile population. The promise of fibril-directed therapies to restore organ function remains despite early disappointments. In this review, we discuss new therapies to tackle AL amyloidosis using a case-based approach.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Disease Management; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Teniposide
PubMed: 34889374
DOI: 10.1182/hematology.2021000305 -
The American Journal of Medicine Apr 2022Light chain (AL) amyloidosis is a potentially fatal disease of monoclonal plasma cells that leads to accumulation of light chain amyloid fibrils, organ damage, and the...
Light chain (AL) amyloidosis is a potentially fatal disease of monoclonal plasma cells that leads to accumulation of light chain amyloid fibrils, organ damage, and the manifestations of clinical disease. Meanwhile, coronavirus disease 2019 (COVID-19) is a disease caused by infection with the severe acute respiratory syndrome coronavirus 2 virus, with the potential to cause severe systemic illness and death. There is significant overlap in the demographics and comorbidities observed in AL amyloidosis and those associated with highest risk for severe morbidity and mortality due to COVID-19. This overlap creates unique challenges in caring for patients with AL amyloidosis, which are further compounded by the immunosuppressive nature of anti-plasma cell therapies, the need for frequent clinical assessments, and the exclusion of AL amyloidosis patients from initial COVID-19 vaccine trials. Herein, we highlight many of the relevant concerns related to COVID-19 and the treatment of AL amyloidosis, summarize a general approach for AL amyloidosis management amidst the ongoing COVID-19 pandemic, and discuss current guidance about COVID-19 vaccination of patients with AL amyloidosis.
Topics: Amyloidosis; COVID-19; COVID-19 Vaccines; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Pandemics
PubMed: 35081378
DOI: 10.1016/j.amjmed.2022.01.005 -
The New England Journal of Medicine Apr 2020
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Incidence; United Kingdom
PubMed: 32294353
DOI: 10.1056/NEJMc1917321 -
Arkhiv Patologii 2021The paper describes an autopsy observation of a 71-year-old male with primary generalized AL amyloidosis lasting about 4 months after its manifestation to the onset of...
The paper describes an autopsy observation of a 71-year-old male with primary generalized AL amyloidosis lasting about 4 months after its manifestation to the onset of death from hepatic and renal failure. Total damage to the liver and spleen, as well as amyloid deposits in the kidneys, adrenal glands, and pancreas were noted.
Topics: Aged; Amyloid; Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Kidney; Liver; Male
PubMed: 33512125
DOI: 10.17116/patol20218301131 -
American Journal of Hematology Jul 2021
Topics: Aged; Bone Marrow; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Multiple Myeloma; Nail Diseases; Nails
PubMed: 33180338
DOI: 10.1002/ajh.26046 -
Vnitrni Lekarstvi 2021Amyloidosis is a rare disorder caused by amyloid deposits in various organs and tissues resulting in vital organ dysfunction, eventually death. There are two forms of...
Amyloidosis is a rare disorder caused by amyloid deposits in various organs and tissues resulting in vital organ dysfunction, eventually death. There are two forms of amyloidosis - systemic, characterized by multiple organs affected, and localized (focal). Localized forms of amyloidosis usually affect urinary bladder, skin and lungs. Pulmonary amyloidosis may be localized or systemic such as diffuse alveolo-septal pulmonary amyloidosis which usually accompanies systemic AL amyloidosis. Other two forms of pulmonary amyloidosis are tracheobronchial and nodular. All three forms are usually detected by accident when patients undergo chest examination for different reasons as most cases of pulmonary amyloidosis are asymptomatic. The prognosis of localized amyloidosis is good with 5-year overall survival being 90,6 %. In our case report we present three patients diagnosed with localized pulmonary amyloidosis at our center. In all cases the diagnoses were made following the resection of affected lung segments with no further treatment needed.
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Lung Diseases; Prognosis
PubMed: 35459379
DOI: No ID Found -
Advances in Therapy Nov 2023Systemic immunoglobulin light chain (AL) amyloidosis is a heterogeneous rare disease driven by a destructive monoclonal gammopathy and typified by misfolded... (Review)
Review
Systemic immunoglobulin light chain (AL) amyloidosis is a heterogeneous rare disease driven by a destructive monoclonal gammopathy and typified by misfolded immunoglobulin light and/or heavy chains which aggregate and deposit in organs as insoluble amyloid fibrils. Disease heterogeneity is driven by the degree of multi-systemic involvement; cardiac, renal, neurological, and gastrointestinal (GI) systems are affected to varying degrees in different patients. While prognosis is primarily driven by hematologic response to treatment and outcomes associated with cardiac events and overall survival, the involvement of the peripheral nervous, hepatic, and GI systems can also have a significant impact on patients. The Amyloidosis Forum ( https://amyloidosisforum.org ) is a public-private partnership between the nonprofit Amyloidosis Research Consortium ( www.arci.org ) and the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research formed to advance drug development for the treatment of systemic amyloid disorders. A series of virtual workshops focused on the development of novel, patient-relevant endpoint components and analytical strategies for clinical trials in AL amyloidosis. This review summarizes the proceedings and recommendations of the Multi-Systemic Working Group which identified, reviewed, and prioritized endpoints relevant to the impacts of AL amyloidosis on the peripheral nervous, hepatic, and GI systems. The Working Group comprised amyloidosis experts, patient representatives, statisticians, and representatives from the FDA, Medicines and Healthcare products Regulatory Agency (MHRA), and pharmaceutical companies. Prioritized neuropathy/autonomic endpoints included a modified form of the Neuropathy Impairment Score (NIS + 7) and the Composite Autonomic Symptom Score (COMPASS-31), respectively. Alkaline phosphatase was identified as the most relevant indicator of liver involvement and disease progression. Following extensive review of potential GI endpoints, the Working Group identified multiple exploratory endpoints. These recommended components will be further explored through evaluation of clinical trial datasets and possible integration into composite endpoint analysis.
Topics: United States; Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Amyloid; Immunoglobulin Light Chains; Liver
PubMed: 37658177
DOI: 10.1007/s12325-023-02637-4 -
Blood Advances Oct 2019Bortezomib and dexamethasone with cyclophosphamide (CyBorD) or melphalan (BMDex) are commonly used primary treatments for light-chain (AL) amyloidosis, but limited data...
Bortezomib and dexamethasone with cyclophosphamide (CyBorD) or melphalan (BMDex) are commonly used primary treatments for light-chain (AL) amyloidosis, but limited data exist on bortezomib with immunomodulatory drug combinations. We report our experience with primary therapy with a bortezomib, lenalidomide, and dexamethasone (VRD) "light" regimen in 34 consecutive patients with AL amyloidosis. The majority (79%) had cardiac involvement, 15% and 23% were Mayo stage 3A and 3B, respectively, and 54% had renal involvement. After the first VRD cycle, 71% of patients achieved a hematologic response (44% at least very good partial response [VGPR]). On intent to treat, 11 (32%) achieved a complete response (of whom 5 of 11 were minimal residual disease [MRD] negative at 10-5), 17 (50%) a VGPR, and 2 (7%) a partial response. The 12-month survival was 73%. Starting lenalidomide dose was 5 mg in 86% of patients. Hematologic toxicity was mild; nonhematologic toxicities included rash (grade 3/4 [16%]), infections (grade ≥3 [12%]), constipation (grade ≥3 [9%]), and peripheral neuropathy (grade 2 [20%]); 37.5% of patients required lenalidomide dose reduction, 27% discontinued lenalidomide, 38% required bortezomib dose reduction, and 12% discontinued bortezomib. We compared VRD to CyBorD in 68 patients matched for Mayo stage and baseline difference between involved minus uninvolved serum free light chain levels, and observed a trend for deeper response at 3 and 6 months with VRD. In conclusion, VRD can be an active regimen for newly diagnosed patients with AL amyloidosis able to induce very deep hematologic responses at the expense of increased toxicity.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bortezomib; Chromosome Aberrations; Dexamethasone; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Lenalidomide; Male; Middle Aged; Treatment Outcome
PubMed: 31648323
DOI: 10.1182/bloodadvances.2019000147