Amyloidosis, primary (Amyloidosis)

Primary Amyloidosis (AL Amyloidosis) – Treatment Overview

Introduction
Primary amyloidosis, also known as AL (amyloid light-chain) amyloidosis, is a rare plasma cell disorder in which misfolded immunoglobulin light chains (produced by abnormal plasma cells in the bone marrow) form insoluble amyloid fibrils that deposit in tissues and organs. The most commonly affected organs are the kidneys, heart, liver, peripheral nerves, and gastrointestinal tract. Untreated, it progresses rapidly and is often fatal, with a median survival of less than 2 years.

The goal of treatment is to suppress the underlying plasma cell clone, stop production of amyloidogenic light chains, and provide organ support.

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Disease-Modifying Therapy

1. Chemotherapy (mainstay of treatment)

• Bortezomib-based regimens (standard):

  • Cyclophosphamide + Bortezomib + Dexamethasone (CyBorD)

    • Bortezomib: 1.3 mg/m² subcutaneous/IV weekly.

    • Cyclophosphamide: 300 mg/m² orally/IV weekly.

    • Dexamethasone: 20–40 mg orally/IV weekly.

• Highly effective in achieving rapid hematologic response.

2. Monoclonal Antibody Therapy

• Daratumumab (anti-CD38 monoclonal antibody):

  • Used alone or in combination with CyBorD.

  • Improves both hematologic and organ response rates.

3. Autologous Stem Cell Transplantation (ASCT)

• Considered in fit patients (younger, limited organ dysfunction).

• High-dose melphalan (200 mg/m² IV) followed by ASCT.

• Can induce long-term remission in selected patients.

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Supportive / Organ-Specific Therapy

Cardiac involvement (restrictive cardiomyopathy)

• Loop diuretics for fluid overload.

• Avoid beta-blockers, ACE inhibitors, and ARBs (often poorly tolerated).

• Anticoagulation for atrial fibrillation (high thrombotic risk).

Renal involvement (proteinuria, nephrotic syndrome, renal failure)

• ACE inhibitors/ARBs may reduce proteinuria (if tolerated).

• Dialysis or renal transplantation in end-stage disease (after controlling plasma cell disorder).

Neuropathy

• Pain management: gabapentin, pregabalin, duloxetine.

GI involvement

• Nutritional support, antidiarrheals, prokinetics if gastroparesis present.

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Prognosis

• Prognosis depends on extent of organ involvement, especially cardiac function.

• With modern therapy, median survival has improved significantly (3–5 years or longer in responders).

• Early diagnosis and treatment initiation are key to improving outcomes.