What is Amyloidosis?

From the Guidelines

Amyloidosis is a group of diseases characterized by the abnormal buildup of amyloid proteins in various tissues and organs, potentially causing organ dysfunction, with AL amyloidosis being one of the more common and severe forms, usually involving the slow proliferation of a bone-marrow-residing plasma cell clone and the secretion of unstable immunoglobulin-free light chains (FLC) that infiltrate peripheral tissues and result in detrimental end-organ damage 1. The management of amyloidosis, particularly AL amyloidosis, is complex and requires early diagnosis to prevent irreversible end-organ damage.

• The hallmark of treatment is early diagnosis before irreversible end-organ damage.
• Treatment decision is transplant-driven, with approximately 20% of patients being eligible for autologous stem cell transplantation (ASCT) with or without bortezomib-based induction 1.
• In the setting of ASCT-ineligibility, bortezomib plays a central role in upfront treatment, with the recent addition of daratumumab to the current emerging standard of care 1.
• The goal of therapy is to achieve deep, durable responses with very close monitoring for early detection of relapse/refractory disease.
• Treatment response monitoring recommendations, toxicity management, and treatment of relapse/refractory disease are crucial components of AL amyloidosis management 1. The importance of early diagnosis and treatment cannot be overstated, as the effectiveness of treatment depends on the extent of organ damage, with better outcomes when started before significant dysfunction occurs.
• Regular monitoring of organ function and response to therapy is necessary to adjust treatment as needed.
• Supportive care is essential for all types of amyloidosis and includes organ-specific treatments such as diuretics for heart failure, dialysis for kidney failure, and nutritional support.

From the Research

Definition of Amyloidosis

• Amyloidosis is a systemic disease characterized by an amyloid deposition process affecting many organs, leading to tissue destruction and progressive disease 2, 3, 4.
• It is a monoclonal plasma cell proliferative disorder, where amyloidogenic monoclonal light chain fragments cause organ dysfunction 4.
• Amyloidosis can be classified into different types, including AL amyloidosis, AA amyloidosis, and others, each with distinct characteristics and treatment approaches 2.

Characteristics of AL Amyloidosis

• AL amyloidosis is a plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure 3.
• It is often associated with monoclonal gammopathy of undetermined significance, multiple myeloma, or Waldenström macroglobulinemia 5.
• The most common target organs are the kidney and heart, with renal amyloidosis manifesting as proteinuria or nephrotic syndrome in many patients 3, 4.

Diagnosis and Treatment

• Diagnosis of amyloidosis requires confirming the diagnosis with tissue biopsy and staining with Congo red, followed by confirmatory typing with mass spectrometry 4.
• Treatment options depend on the disease staging, frailty, and co-morbidities, and may include autologous hematopoietic cell transplantation, chemotherapy, and novel agents such as bortezomib and lenalidomide 2, 4, 5, 6.
• The goal of treatment is to achieve complete hematologic response and preserve or improve organ function, with ongoing research focused on developing new therapies to target amyloid deposits directly 4, 6.