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Rituximab and Alemtuzumab for Chronic Lymphocytic Leukemia: Basic Results and Pharmacokinetics

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Chemotherapy for Leukemia

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Abstract

Rituximab is a chimeric anti-CD20 monoclonal antibody (mAb) and the first mAb to be approved for use in the treatment of cancer. The proposed mechanisms of action of rituximab include antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and induction of apoptosis. The influences of CD20 expression level, circulating soluble CD20, Fcγ receptor (FcγR) polymorphisms, complement regulatory proteins, and C1qA-276 polymorphisms on susceptibility and resistance to rituximab have been previously described. In a pharmacokinetic study, from the first to the fourth or eighth weekly dose of rituximab, post-infusion serum concentrations increased and steady-state serum concentrations were not reached. The combined use of rituximab and fludarabine, bendamustine, lenalidomide, or histone deacetylase inhibitors may be one of the optimal solutions for overcoming rituximab resistance in the treatment of chronic lymphocytic leukemia (CLL). The characteristic toxicities of rituximab are infusion reactions, late-onset neutropenia, hepatitis B virus reactivation, and opportunistic infections.

Alemtuzumab is a humanized anti-CD52 mAb and the first mAb to be approved for use in the treatment of CLL. The proposed mechanisms of action of alemtuzumab include ADCC, CDC, and induction of apoptosis. The influences of CD52 expression level, circulating soluble CD52, FcγR polymorphisms, and cytogenetic abnormalities on susceptibility and resistance to alemtuzumab have been previously described. In a pharmacokinetic study, systemic clearance decreased with repeated administration of alemtuzumab due to decreased receptor-mediated clearance. The combined use of alemtuzumab and fludarabine, cyclophosphamide, or rituximab may be one of the optimal solutions for overcoming alemtuzumab resistance in the treatment of CLL. The characteristic toxicities of alemtuzumab are infusion reactions, opportunistic infections, and cytopenia.

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  1. Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan

    Katsuki Sugiyama

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    Takanori Ueda

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Sugiyama, K. (2017). Rituximab and Alemtuzumab for Chronic Lymphocytic Leukemia: Basic Results and Pharmacokinetics. In: Ueda, T. (eds) Chemotherapy for Leukemia. Springer, Singapore. https://doi.org/10.1007/978-981-10-3332-2_5

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