Initial Experience with Lecanemab and Lessons Learned in 71 Patients in a Regional Medical Center.

BACKGROUND AND OBJECTIVES

On July 6, 2023 the U.S. Food and Drug Administration approved the anti-amyloid monoclonal antibody lecanemab (Leqembi®) for treatment of patients with mild cognitive impairment or mild dementia due to Alzheimer's disease (AD). Our early experience and lessons learned with lecanemab in a regional community medical center are described.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational study highlights the first 71 patients treated with lecanemab at our multidisciplinary Norton Neuroscience Institute Memory Center. All patients had positive cerebrospinal fluid biomarkers for AD and underwent at least 1 lecanemab infusion. Two patients had additional amyloid PET scans which were positive.

RESULTS

The mean age was 72 years (49-90 years), and 44 (62%) patients were female. Most were Caucasian (68 [96%]), and 54 [76%] were referred to our Memory Center by their primary care provider. Comorbidities were common, including hypertension (34 [48%]), hypercholesterolemia (51 [72%]), diabetes mellitus (17 [24%]), and cardiovascular disease excluding hypertension (22 [31%]). The mean body mass index was 27.0 (range: 17.8-45.0). A total of 36 (51%) patients were heterozygous for the ApoE4 genotype, and 9 (13%) were homozygous. A total of 61 [86%] patients had been treated with donepezil; 40 (56%) patients had received memantine. Of the 50 patients who completed 1 or more safety monitoring brain MRIs following infusion, 12 (24%) had amyloid-related imaging abnormalities (ARIA) detected: solitary ARIA-H (hemorrhage) in 5, solitary ARIA-E (edema) in 3, and both ARIA-H and ARIA-E in 4. Of the 12 patients with ARIA, 9 were asymptomatic, 4 were homozygous for the ApoE4 genotype, and 6 were heterozygous for the ApoE4 genotype. Of the 9 who were homozygous for the ApoE4 genotype in this study, 4 (44%) had evidence of ARIA. Of the 36 who were heterozygous for the ApoE4 genotype, 6 (17%) were diagnosed with ARIA. Twenty-six (37%) patients experienced infusion reactions after their first lecanemab infusion: headaches (12 patients) and shaking/chills/rigors (11 patients) were most common. Twenty-three (88%) of these 26 patients reported the side effects either at the infusion center or within the first 24 hours post-infusion. One patient died shortly after the first lecanemab infusion of a myocardial infarction. It is uncertain whether or not this death was related to lecanemab treatment.

CONCLUSION

Through our early experience with lecanemab, we have recognized several areas of improvement which have clarified and enhanced the lecanemab infusion experience.