Monoclonal antibodies as targeted therapy in hematologic malignancies in older adults

Abstract

Background: Biological agents are proving to be increasingly useful and exciting additions to the antineoplastic armamentarium, but many clinicians are unfamiliar with the properties of these types of agents.

Objectives: This review focuses on monoclonal antibodies (MAbs) that are used in the treatment of hematologic malignancies. Our goal was to provide the reader with information on trials that led to US Food and Drug Administration (FDA) approval of commonly used MAbs in hematologic malignancies, including their mechanisms of action and pharmacokinetics, with specific emphasis on use in elderly patients; we also present data on toxicities and precautions to be aware of when administering these drugs.

Methods: Materials for this review were gathered based on a computerized literature search (English-language articles only) using the PubMed database covering the period January 1998 to December 2005. Search terms used included the following: elderly, monoclonal antibodies, and neoplasms.

Results: Alemtuzumab is a recombinant DNA-derived, humanized MAb directed against the CD52 B-cell antigen. It is indicated for the treatment of B-cell chronic lymphocytic leukemia (CLL) in patients who have been treated with alkylating agents and who have failed to respond to fludarabine therapy. Gemtuzumab ozogamicin is an MAb conjugated with a cytotoxic antitumor antibiotic, calicheamicin. It has been approved for use in patients with CD33-positive acute myeloid leukemia (AML) in first relapse who are aged > or =60 years and who are not considered candidates for other cytotoxic chemotherapy. Rituximab, one of the first MAbs approved by the FDA for use in human cancers, is an antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. It is extensively used in the treatment of B-cell malignancies, such as CLL, and non-Hodgkin's lymphomas (NHLs), such as follicular lymphoma and diffuse large B-cell lymphoma.

Conclusions: It is noteworthy that while there have been a number of studies using these agents in the younger population, there continues to be a paucity of clinical trials targeting the elderly patient in particular; this continues to be an area of research interest. More clinical studies of these agents--conducted specifically in elderly patients with CLL, NHL, AML, and other hematologic malignancies--are needed.