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

Michela Montagna, Marco Montillo, Maria A. Avanzini, Carmine Tinelli, Alessandra Tedeschi, Livia Visai, Francesca Ricci, Eleonora Vismara, Enrica Morra, Mario Regazzi

Research output: Contribution to journalArticle

Abstract

Alemtuzumab serum levels and clinical response after subcutaneous administration (10 mg 3 times/week for six weeks) have been explored in 29 chronic lymphocytic leukemia patients receiving the monoclonal antibody as consolidation. Serum concentrations after each administration gradually increased during the first week and more markedly during weeks 2 and 3, approaching the steady-state at week 6. Absorption continued slowly through the tissues for about 2- 3 weeks after the last administration, starting to decrease thereafter. Difference between Responders and Non-responders was statistically significant: maximal concentration (Cmax) was 1.69 μg/mL vs. 0.44 μg/mL; concentration before subcutaneous administration (Cpre-dose) on day 15 was 0.7 vs. 0.21 μg/mL, area under curve (AUC0-12h) was 11.09 vs. 2.26 μg x h/mL for Responders and Non-responders, respectively. Higher systemic exposure to alemtuzumab correlated with a better clinical response and minimal residual disease. Results suggest that an adjusted schedule according to serum level could improve clinical outcome of patients receiving subcutaneous alemtuzumab.

Original languageEnglish
Pages (from-to)932-936
Number of pages5
JournalHaematologica
Volume96
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Alemtuzumab
  • Chronic lymphocytic leukemia
  • Pharmacokinetics

ASJC Scopus subject areas

  • Hematology

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