Plasma alemtuzumab levels in patients with chronic lymphocytic leukemia treated with alemtuzumab combined with chemotherapy reflect the efficacy of the treatment: a hypothesis

Abstract

In the HOVON68 trial comparing subcutaneous low-dose alemtuzumab (LD-A) used together with fludarabine (F) and cyclophosphamide (C) with FC alone in high-risk chronic lymphocytic leukemia (CLL), LD-AFC resulted in significantly more clinical and molecular responses than FC, but also in more opportunistic infections. In a subgroup analysis of alemtuzumab trough levels during treatment by a sensitive enzyme-linked immunosorbent assay (ELISA) method, detectable levels were found in 4/6 complete and 0/3 partial responders. A relationship between alemtuzumab plasma levels, response and duration of lymphocytopenia was evident. We hypothesize that following combination therapy, the response may not be a function of the alemtuzumab levels, but the opposite, that plasma alemtuzumab levels are a function of the efficacy of the entire treatment, and the fewer leukemic target cells that are remaining, the higher are the levels of plasma alemtuzumab. This concept may well provide a guide for alemtuzumab dosage in future trials.

Keywords::

• Alemtuzumab
• pharmacokinetics
• immunochemotherapy
• chronic lymphocytic leukemia
• CLL
• Campath

Acknowledgements

This publication is supported by the Rigshospitalet, Copenhagen, Denmark; The Danish Cancer Society; The Novo Nordisk Foundation; The Danish Cancer Research Foundation; The Axel Meyer Nielsen and Vetsera Meyer Nielsen foundation; and the John and Birthe Meyer Foundation. The HOVON68 study was supported by an unrestricted grant from Genzyme Corporation including donation of the alemtuzumab antibody.

Potential conflict of interest:

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