Maintenance Lecanemab Following Donanemab-Induced Amyloid Clearance: A Hypothesis-Generating Commentary on Sequential Anti-Amyloid Therapy in Early Alzheimer Disease

The introduction of amyloid-targeting monoclonal antibodies has transformed the therapeutic landscape of early Alzheimer disease (AD). Donanemab (Kisunla) and lecanemab (Leqembi) have demonstrated slowing of cognitive decline through reduction of beta-amyloid burden. A unique feature of donanemab is its biomarker-guided discontinuation strategy, allowing treatment cessation once amyloid plaque burden falls below predefined thresholds. In contrast, lecanemab is approved for ongoing maintenance therapy following an initial treatment phase. This commentary proposes a novel, off-label treatment paradigm in which patients who successfully complete donanemab therapy and achieve amyloid clearance subsequently transition to maintenance lecanemab, including weekly subcutaneous administration, with the goal of preventing amyloid reaccumulation. Discussion includes mechanistic rationale, safety considerations, and a representative patient case illustrating implementation of this approach. Prospective studies are needed to determine whether sequential anti-amyloid therapy can sustain amyloid negativity and prolong clinical benefit.