Relationship between pharmacokinetic profile of subcoutaneously administered alemtuzumab and clinical response in patients with chronic lymphocytic leukemia

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BlankRelationship between pharmacokinetic profile of subcoutaneously

administered alemtuzumab and clinical response in patients with chronic

lymphocytic leukemia.

M Montagna, M Montillo, MA Avanzini, C Tinelli, A Tedeschi, L Visai, F Ricci, E

Vismara, E Morra, and M Regazzi

Haematologica, February 17, 2011; .

Alemtuzumab serum levels and clinical response after subcutaneous administration

(10 mg thrice/week for six weeks) have been explored in 29 Chronic Leukemia

Lynphocitic patients receiving the monoclonal antibody as consolidation. Serum

concentrations after each administration gradually increased during the first

week and more markedly during weeks two and three, approaching the steady-state

at 6th week. Absorption continued slowly through the tissues for about 2-3 weeks

after the last administration, starting to decrease thereafter.Difference

between Responder and Non-responders was statistically significant: Cmax was

1.69 mcg/mL vs 0.44 mcg/mL; Cpre-dose before sc administration, on day 15, was

0.7 vs 0.21mcg/mL, total systemic exposure to Alemtuzumab (Area Under Curve,AUC

0-12h) was 11.09 vs 2.26 mcg X h/mL for Responders and Non-responders group,

respectively. Higher systemic exposure to Alemtuzumab correlated with a better

clinical response and minimal residual disease.Results suggest that adjusted

schedule according to serum level could improve clinical outcome of patients

receiving sc Alemtuzumab.

PMID: 21330330