Lymphocyte subset dynamics following alemtuzumab administration in the CARE-MS I trial

OBJECTIVE: Alemtuzumab, a humanised monoclonal antibody that alters the circulating lymphocyte pool. In CARE-MS I alemtuzumab reduced relapse rate by 55% compared to SC IFNB-1a (p<0.0001). We describe effects of alemtuzumab on lymphocyte subsets in CARE-MS I. METHODS: CARE-MS I, a 2-year, randomized, rater-blinded trial comparing alemtuzumab to SC IFNB-1a in treatment-naïve, relapsing-remitting MS patients (n=563). Alemtuzumab was administered intravenously 12mg/day on 5 days at study start and 3 days 12 months later. Blood counts were tested monthly. Circulating lymphocytes were phenotyped by flow cytometry quarterly for all patients and at months 1 and 13 for alemtuzumab patients. RESULTS: Alemtuzumab depleted circulating B- and T-lymphocytes following each course, with lowest values recorded at first post-treatment measurement, 1 month later: mean % baseline values for CD4+, CD8+, and CD19+ subsets were 4.7%, 14.6%, and 10.5%, respectively. Mean CD4+ and CD8+ counts returned to 31% and 53% of baseline values, respectively, 12 months after first course, and 116% and 107% of pre-second course values 12 months later. Six months following first course, mean CD19+ counts returned to 112% of baseline values; 12 months following second course, mean CD19+ counts returned to 109% of pre-second course values. The proportion of patients with CD4 reconstitution to ≥200×10^6/L was 82.4% 12 months after first course and 87.2% 12 months after second course. CONCLUSIONS: Alemtuzumab-induced lymphocyte depletion and repopulation occurred after each alemtuzumab course, with B-cells recovering sooner than T-cells. There was no cumulative reduction in lymphocyte repopulation capacity with a second alemtuzumab administration.