What is the treatment for Amyloid Light-chain (AL) amyloidosis?

Treatment for AL Amyloidosis

Daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) is the current standard of care and preferred first-line treatment for newly diagnosed AL amyloidosis. 1, 2

First-Line Treatment Options

Preferred Regimen

• Daratumumab-CyBorD: FDA-approved specifically for AL amyloidosis
  • Produces very good partial responses or better in 78.5% of patients (vs. 49.2% with CyBorD alone) 1
  • Only FDA-approved agent specifically for AL amyloidosis treatment 1

Alternative First-Line Options

• CyBorD alone: For patients who cannot receive daratumumab 1
• Bortezomib-melphalan-dexamethasone (BMD): Alternative regimen 1
• High-dose melphalan with autologous stem cell transplantation (HDM/SCT):
  • For highly selected patients (only ~25% of newly diagnosed patients are eligible) 1
  • Treatment-related mortality ~3% in experienced centers 1
  • Offers possibility of long-lasting remission and high organ response rates 1

Special Considerations

• Advanced cardiac involvement: Patients with NT-proBNP >8,500 pg/mL may receive single-agent daratumumab with minimal dexamethasone to reduce cardiotoxicity 1

Treatment Response Assessment

Hematologic Response Criteria 1

• Complete response (CR): Absence of amyloidogenic light chains + normal free light chain ratio
• Very good partial response (VGPR): Difference between involved and uninvolved free light chains <40 mg/L
• Partial response (PR): ≥50% decrease in difference between involved and uninvolved free light chains
• No response (NR): <50% decrease in difference between involved and uninvolved free light chains

Organ Response Criteria 1

• Cardiac: Decrease in NT-proBNP by >30% and <300 ng/L (if baseline NT-proBNP >650 ng/L)
• Renal: ≥30% decrease in proteinuria or drop below 0.5 g/24h without kidney function decline
• Hepatic: 50% decrease in abnormal alkaline phosphatase or ≥2 cm decrease in liver size

Monitoring Schedule

• Hematologic response: Usually observed within 3-6 months of treatment initiation 1
• Organ response: Generally observed 6-12 months after hematologic response 1
• Monthly monitoring during initial treatment should include:
  • Complete blood count
  • Basic biochemistry
  • NT-proBNP and troponin
  • Serum-free light chain quantification 2

Potential Treatment Toxicities

Cardiac Toxicities of Common Agents 1

• Daratumumab: Cardiac failure (12%, grade 3-4 in 6%), cardiac arrhythmia (8%, grade 3-4 in 2%), atrial fibrillation (6%, grade 3-4 in 2%)
• Bortezomib: Grade 3 heart failure in 6.4%, >10% decrease in LVEF in 23%
• Corticosteroids: Peripheral edema, pulmonary edema, fluid overload
• Cyclophosphamide: Myocarditis, pericardial effusion, arrhythmias, heart failure

Common Pitfalls and Caveats

1. Accurate diagnosis is crucial: AL amyloidosis requires tissue biopsy showing amyloid deposits with Congo red staining and apple-green birefringence 2

2. Medication cautions:

   • Avoid digoxin and calcium channel blockers due to potential toxicity 2
   • Use diuretics cautiously to prevent overdiuresis and volume contraction 2

3. Treatment selection considerations:

   • Cardiac involvement is a major determinant of risk and treatment eligibility 1
   • Treatment should be guided by patient's functional status, disease stage, and degree of organ dysfunction 3

4. Response assessment timing:

   • Don't expect immediate organ response; it typically follows hematologic response by several months 1
   • Continue treatment despite initial worsening of cardiac biomarkers, which can occur transiently 1

AL amyloidosis treatment has advanced significantly with the approval of daratumumab-based regimens, offering improved outcomes for patients with this challenging disease. Early diagnosis and prompt initiation of appropriate therapy are essential to prevent irreversible organ damage and improve survival.