What are the new treatment options for cardiac amyloidosis?

New Treatment Options for Cardiac Amyloidosis

The most effective new treatments for cardiac amyloidosis include tafamidis for ATTR cardiomyopathy and daratumumab-based regimens for AL amyloidosis, both of which have demonstrated significant reductions in cardiovascular mortality. 1, 2

Types of Cardiac Amyloidosis and Their Specific Treatments

ATTR Cardiac Amyloidosis (ATTR-CM)

FDA-Approved Treatments

• Tafamidis: First-in-class transthyretin stabilizer and currently the only FDA-approved treatment for ATTR-CM 3
  • Dosing options:
    • VYNDAQEL 80 mg orally once daily, OR
    • VYNDAMAX 61 mg orally once daily 3
  • Efficacy: Significantly reduces cardiovascular mortality and cardiovascular-related hospitalizations 3, 4
  • Long-term benefits: Patients receiving continuous tafamidis showed substantially better survival (HR 0.59,95% CI 0.44-0.79, p<0.001) compared to those who started on placebo and later switched to tafamidis, highlighting the importance of early diagnosis and treatment 5
  • Safety profile: Well-tolerated with no significant side effects reported in clinical trials 1

Emerging Therapies for ATTR-CM

• TTR Gene Silencing Approaches: Suppress TTR protein production 1, 2
• Acoramidis: New TTR stabilizer showing promise in clinical trials 1
• Anti-TTR Fiber Antibodies: Target existing amyloid deposits 2
• Combination Therapy: Future treatment may involve concurrent administration of TTR silencing and stabilizing agents 6

AL Cardiac Amyloidosis (AL-CA)

Current Standard of Care

• Daratumumab combined with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD): First-line treatment achieving high rates of deep hematologic responses 1, 2
• CyBorD alone: Alternative for patients who cannot tolerate daratumumab 1
• High-dose melphalan followed by autologous stem cell transplantation (HDM/SCT): Option for eligible patients without significant cardiac involvement 1
  • Outcomes: 70% achieve very good partial hematologic response or better
  • Survival: Median >15 years in those achieving complete response

Monitoring Treatment Response

ATTR-CM Response Markers

• Circulating markers: Prealbumin, cardiac troponins, natriuretic peptides, kidney function 6
• Imaging markers: Echocardiographic global longitudinal strain and CMR extracellular volume fraction 6
• Clinical metrics: Functional status, hospitalizations, and survival 6

AL-CA Response Markers

• Monthly monitoring: CBC, biochemistry, NT-proBNP, troponin, and serum-free light chain quantification 1
• Imaging: Echocardiography with strain measurements every 6 months 1
• Goal: Very good partial response or better on hematologic parameters 1

Advanced Therapies for End-Stage Disease

• Heart transplantation: Considered for end-stage disease 1
• Combined heart-liver transplantation: For ATTRv (hereditary form) 1
• Liver transplantation: Can cure the disease process as TTR protein is synthesized in the liver 1
  • Outcomes: 5-year survival rate of 50-80% for combined heart and liver transplantation

Treatment Challenges and Considerations

Economic Considerations

• Cost concerns: Tafamidis was the single most expensive cardiovascular drug when approved in 2019 6
  • Cost-effectiveness analysis suggested $880,000 per quality-adjusted life-year gained
  • AHA/ACC/HFSA guidelines state tafamidis provides "low economic value" despite Class 1 recommendation 6

Treatment-Related Toxicities

• Cardiac toxicities of AL-CA treatments 1:
  • Proteasome inhibitors: Heart failure (6.4%), LVEF reduction (23%)
  • Immunomodulatory agents: Paradoxical increase in cardiac biomarkers
  • Daratumumab: Cardiac failure (12%), arrhythmias (8%)

Access to Care

• Multidisciplinary approach: Management requires collaboration between cardiologists, hematologists, neurologists, nephrologists, and palliative care specialists 1, 2
• Telehealth: Emerging as a solution to improve access to amyloidosis specialists, particularly for patients in rural or underserved areas 6

Key Takeaways

1. Early diagnosis and treatment initiation are crucial for improving outcomes in cardiac amyloidosis 5
2. Treatment should be tailored to the specific type of amyloidosis (ATTR vs. AL)
3. Novel therapies targeting various points in the amyloidogenic cascade are in development 2
4. Multidisciplinary care is essential for optimal management 1, 2