Which specialist manages amyloidosis?

Management of Amyloidosis Requires a Multidisciplinary Specialist Team

Amyloidosis management requires a coordinated multidisciplinary team approach led by specialists specific to the amyloid type and affected organs, with cardiologists and hematologists playing central roles for cardiac amyloidosis. 1

Types of Amyloidosis and Lead Specialists

AL Amyloidosis

• Primary specialist: Hematologist-oncologist
• The hematologist guides evaluation when monoclonal protein testing is abnormal to determine if findings represent:
  • Spurious results due to kidney dysfunction
  • Monoclonal gammopathy of uncertain significance (MGUS)
  • True AL amyloidosis
  • Multiple myeloma 1
• Treatment typically involves proteasome inhibitor-based chemotherapy with daratumumab and, when feasible, autologous stem cell transplantation 2

ATTR Amyloidosis

• Primary specialist: Cardiologist (for cardiac ATTR)
• Manages disease-modifying therapies such as tafamidis (80 mg VYNDAQEL or 61 mg VYNDAMAX daily) 3
• Neurologist may lead for predominantly neurologic ATTR presentations

Multidisciplinary Collaboration Requirements

Cardiologist-Hematologist Collaboration

Collaboration is essential for:

1. Interpretation of abnormal monoclonal protein screens
2. Monitoring for cardiotoxicity of AL amyloidosis therapies
3. Assessment of cardiovascular fitness for high-dose melphalan with autologous stem cell transplantation
4. Identification of candidacy for heart transplantation and post-transplant management 1

Nephrologist Involvement

Nephrologists provide critical input for:

• Managing nephrotic syndrome
• Managing cardiorenal syndrome
• Addressing metabolic complications of chronic kidney disease
• Managing nephrotoxic effects of amyloidosis treatments
• Decisions about kidney biopsy and interpretation
• Preparation for kidney replacement therapy 1

Gastroenterologist Involvement

Referral to gastroenterology is indicated for:

• Symptoms not responding to dietary adjustments or over-the-counter medications
• Significant malnutrition or unexplained weight loss
• Need for endoscopy/colonoscopy for biopsies
• Management of GI complications (malabsorption, bacterial overgrowth, severe nausea/vomiting) 1

Diagnostic Approach

AL Amyloidosis

Diagnosis requires:

1. Demonstration of tissue amyloid deposits (biopsy)
2. Evidence of plasma cell dyscrasia
   • Serum free light chains
   • Bone marrow biopsy
   • Serum and urine immunofixation electrophoresis 1

ATTR Amyloidosis

Can be diagnosed non-invasively with:

• Positive bone scintigraphy (Perugini grade 2-3)
• Absence of monoclonal protein
• TTR gene sequencing to differentiate hereditary from wild-type ATTR 4

Treatment Coordination

AL Amyloidosis

• Hematologist directs plasma cell-directed therapy
• Daratumumab + CyBorD (cyclophosphamide, bortezomib, dexamethasone) is standard first-line therapy 4
• Cardiologist manages cardiac complications and monitors for treatment cardiotoxicity

ATTR Amyloidosis

• Cardiologist typically manages TTR stabilizer therapy:
  • Tafamidis (80 mg VYNDAQEL or 61 mg VYNDAMAX daily) 4, 3
  • Acoramidis (Attruby) as an alternative first-line option 4

Advanced Therapies

For end-stage disease, specialists coordinate:

• Heart transplantation for selected patients with advanced heart failure
• Combined heart-liver transplantation for hereditary ATTR
• Combined heart-kidney transplantation for patients with significant renal involvement 1

Common Pitfalls in Amyloidosis Management

1. Delayed diagnosis: Symptoms are often nonspecific and vague, leading to delayed recognition
2. Misdiagnosis: Presence of MGUS in elderly patients with ATTR can lead to misdiagnosis as AL amyloidosis
3. Treatment toxicity: AL amyloidosis patients have poor treatment tolerance due to organ dysfunction
4. Inadequate coordination: Failure to involve all relevant specialists can lead to suboptimal care

Conclusion

The complexity of amyloidosis management necessitates a multidisciplinary approach centered at specialized amyloidosis centers whenever possible. Early referral to such centers is associated with improved outcomes through timely diagnosis, appropriate treatment initiation, and access to clinical trials 5, 6.