Amyloidosis

Amyloidosis – Treatment Overview

Introduction
Amyloidosis refers to a group of disorders caused by extracellular deposition of misfolded proteins in the form of insoluble amyloid fibrils. These deposits disrupt normal tissue architecture and impair organ function. Amyloidosis may be systemic (multi-organ) or localized, with clinical manifestations depending on the organs involved (kidney, heart, liver, GI tract, nerves).

The main types of systemic amyloidosis are:

• AL (light-chain) amyloidosis: Due to plasma cell dyscrasia (e.g., multiple myeloma).

• AA amyloidosis: Secondary to chronic inflammatory conditions (e.g., rheumatoid arthritis, TB).

• ATTR amyloidosis: Transthyretin-related, either hereditary (hATTR) or wild-type (wtATTR).

• Other rare types (Aβ2M in dialysis-related amyloidosis, localized forms).

Treatment is cause-specific, aiming to reduce amyloid production, support affected organs, and improve survival.

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Treatment by Amyloidosis Type

1. AL Amyloidosis (Immunoglobulin Light Chain)

• Goal: Suppress plasma cell clone producing amyloidogenic light chains.

• Chemotherapy (similar to myeloma):

  • Bortezomib + Cyclophosphamide + Dexamethasone (CyBorD) regimen is standard.

  • Lenalidomide or Daratumumab may be added in selected cases.

• Autologous stem cell transplantation (ASCT): Considered in eligible patients with good performance status and limited organ dysfunction.

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2. AA Amyloidosis (Secondary / Reactive)

• Goal: Control underlying chronic inflammatory disease.

• Anti-inflammatory or immunosuppressive therapy (e.g., biologics for RA, anti-TNF or IL-6 inhibitors).

• Antibiotic therapy for chronic infections (e.g., TB).

• Colchicine (especially effective in familial Mediterranean fever).

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3. ATTR Amyloidosis (Transthyretin-Related)

• TTR Stabilizers:

  • Tafamidis 61 mg daily (first-line for cardiac ATTR).

  • Diflunisal 250 mg twice daily (off-label, limited by NSAID toxicity).

• Gene Silencing Therapies (mainly hATTR with neuropathy, also cardiac benefit):

  • Patisiran (siRNA) IV every 3 weeks.

  • Inotersen (antisense oligonucleotide) weekly SC injection.

  • Vutrisiran (next-gen siRNA) every 3 months SC.

• Liver transplant: Rarely used now, formerly standard for hereditary ATTR.

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4. Dialysis-Related Amyloidosis (β2-microglobulin)

• Improved with use of high-flux dialysis membranes and renal transplantation.

• Symptomatic treatment for joint and bone involvement.

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Organ-Specific / Supportive Management

• Renal involvement: Diuretics, salt restriction, dialysis if ESRD develops.

• Cardiac involvement: Loop diuretics for volume overload; anticoagulation for atrial fibrillation; avoid beta-blockers/ACE inhibitors if poorly tolerated (restrictive physiology).

• Neuropathy: Neuropathic pain agents (gabapentin, pregabalin, duloxetine).

• GI involvement: Dietary modifications, nutritional support, antidiarrheal agents.

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Prognosis

• AL amyloidosis: Untreated survival <1–2 years; outcomes improved significantly with modern therapy.

• AA amyloidosis: Prognosis depends on control of underlying disease.

• ATTR amyloidosis: Slowly progressive but treatable; tafamidis and RNA-silencing therapies improve survival.

• β2M amyloidosis: Improved with renal transplantation.