Is an Amyloid PET scan still necessary before starting Lecanemab (anti-amyloid therapy) in a patient with recent memory decline and positive serum p tau 217?

Amyloid PET Scan Requirement Before Starting Lecanemab

A positive serum p-tau217 test is sufficient biomarker evidence of amyloid pathology to initiate lecanemab therapy in a 70-year-old patient with recent memory decline, without requiring an additional amyloid PET scan. 1, 2

Biomarker Requirements for Anti-Amyloid Therapy

• Lecanemab FDA labeling requires confirmation of amyloid beta pathology prior to initiating treatment, but does not specify which biomarker test must be used 3
• According to current guidelines, biomarker evidence of amyloid pathology can be established through either positive amyloid PET imaging OR positive CSF biomarkers 1
• Blood-based biomarkers, particularly plasma p-tau217, are increasingly being recognized as reliable indicators of amyloid pathology with high accuracy (AUC 0.92-0.98) for predicting amyloid status 1, 2
• Plasma p-tau217 is considered one of the most promising blood biomarkers for detecting amyloid pathology, with performance comparable to CSF tests for classifying amyloid PET status 1

Clinical Decision Algorithm

1. Assess biomarker evidence:

   • Patient already has positive serum p-tau217 test 1
   • This test has demonstrated high accuracy (AUC 0.92-0.98) in predicting amyloid status 1

2. Consider patient factors:

   • 70-year-old with recent memory decline (consistent with early AD) 1
   • Already has positive blood biomarker evidence 1

3. Treatment eligibility assessment:

   • Lecanemab is indicated for patients with mild cognitive impairment or mild dementia stage of disease 3
   • Requires confirmation of amyloid pathology, which has been established via p-tau217 1, 3

Safety Considerations

• Before starting lecanemab, a baseline brain MRI (not amyloid PET) is required to assess for contraindications to therapy 3, 1
• Regular MRI monitoring is mandatory during treatment to detect ARIA (Amyloid-Related Imaging Abnormalities) 1, 4
• MRI should be obtained prior to the 5th, 7th, and 14th infusions of lecanemab 1

Important Caveats

• While amyloid PET has traditionally been used in clinical trials, it is expensive, requires specialized equipment and personnel, and has limited availability 1
• Blood-based biomarkers like p-tau217 offer advantages in terms of accessibility, cost, and patient acceptance 1, 2
• The FDA label for lecanemab does not specify which biomarker test must be used, only that amyloid pathology must be confirmed 3
• If there are atypical clinical features or diagnostic uncertainty, an amyloid PET scan might still be considered, but is not mandatory when p-tau217 is already positive 1

Conclusion

For this 70-year-old patient with memory decline and positive serum p-tau217, proceeding with lecanemab treatment without an additional amyloid PET scan is appropriate and consistent with current guidelines and FDA labeling. The positive p-tau217 result provides sufficient biomarker evidence of amyloid pathology to initiate therapy. However, a baseline brain MRI is essential before starting treatment to assess for contraindications and establish a baseline for monitoring ARIA during therapy.