From the Guidelines
Definition of Amyloidosis
Amyloidosis is a group of rare, heterogeneous disorders characterized by the deposition of insoluble amyloid fibrils in various tissues and organs, leading to cellular damage and organ dysfunction 1, 2.
Key Characteristics
The condition can be primary, secondary, or hereditary, with primary amyloidosis often associated with plasma cell dyscrasias, such as multiple myeloma 1. Systemic amyloidoses constitute disorders of diverse etiologies involving the synthesis and abnormal extracellular deposition of misfolded proteins in various organs with resultant damage 1.
Types of Amyloidosis
There are several types of amyloidosis, including systemic and localized light chain (AL) amyloidosis, which occurs de novo as primary or in concomitance with myeloma 2. AL amyloidosis is among the more common and more severe of the amyloidoses, usually involving the slow proliferation of a bone-marrow-residing plasma cell (PC) clone and the secretion of unstable immunoglobulin-free light chains (FLC) that infiltrate peripheral tissues and result in detrimental end-organ damage 3.
Organs Involved
Organs involved usually include kidneys, heart, gastrointestinal (GI) tract, liver, and nervous system, whereby undoubtedly cardiac involvement is the main driver of disease prognosis and mortality 1.
Importance of Early Diagnosis
Given that more than 69% of patients already have more than one organ involved at the time of diagnosis, it becomes vital to not only diagnose AL amyloidosis early, but to also effectively control plasma cell dyscrasias and thus halt escalating organ damage 1.
Treatment
Treatment may involve medications, with the goal of achieving deep, durable responses and very close monitoring for early detection of relapse/refractory disease 3. Autologous stem cell transplantation (ASCT) remains the standard of care and first-line treatment in a small proportion of patients, while bortezomib plays a central role in upfront treatment for ASCT-ineligible patients 1, 3.
From the FDA Drug Label
VYNDAQEL and VYNDAMAX are prescription medicines used to treat adults with cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) to reduce death and hospitalization related to heart problems.
Amyloidosis is not directly defined in the provided drug labels. However, based on the context, it can be inferred that amyloidosis refers to a condition characterized by the accumulation of amyloid, a type of protein, in the body, which can lead to various health problems, including cardiomyopathy. The FDA drug label does not provide a clear definition of amyloidosis, and any conclusion drawn would be indirect. Given the information provided in the drug labels, no conclusion can be drawn about what amyloidosis is. 4, 5, 6
From the Research
Definition of Amyloidosis
- Amyloidosis is a heterogeneous group of diseases characterized by the deposition of amyloid, a fibrillar aggregate that can lead to cell damage and organ dysfunction 7, 8, 9.
- It is caused by the extracellular deposition of insoluble fibrils with a beta-pleated sheet configuration, resulting from protein misfolding abnormalities 8.
- Amyloidosis can be classified into different types, including primary, secondary, and familial amyloidosis, and can affect various organs such as the heart, liver, kidney, skin, eyes, lungs, and nervous system 8, 10.
Characteristics of Amyloidosis
- Amyloid deposits can occur locally in tissues or may involve various organs, resulting in a wide range of clinical manifestations 8, 11.
- The deposition of amyloid can lead to organ dysfunction and damage, and can be associated with various diseases such as Alzheimer's disease, multiple myeloma, and chronic inflammation 7, 9.
- The diagnosis of amyloidosis can be challenging, and requires the participation of many clinical and laboratory specialties 10.
Types of Amyloidosis
- There are several types of amyloidosis, including AL, AA, ALECT2, and ATTR, each with distinct characteristics and clinical manifestations 8, 10.
- The classification of amyloidosis is based on the amyloid protein type, and determination of the protein type is imperative before specific therapy can be implemented 10.
- Some types of amyloidosis, such as AL, are associated with plasma cell dyscrasias, while others, such as ATTR, are associated with aging or genetic mutations 8, 10.