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Lymphoma

Radiolabeled and Native Antibodies and the Prospect of Cure of Follicular Lymphoma

^aFred Hutchinson Cancer Research Center, Seattle, Washington, USA; ^bService of Nuclear Medicine, University Hospital of Lausanne, Lausanne, Switzerland; ^cService of Nuclear Medicine, University Hospital of Geneva, Geneva, Switzerland; ^dDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA; ^e Multidisciplinary Oncology Center, University Hospital of Lausanne, Lausanne, Switzerland

Key Words. Follicular lymphoma • Radioimmunotherapy • Antitumor antibodies • Chemotherapy • Cytokines • Combination therapy

Correspondence: Franz Buchegger, M.D., Service of Nuclear Medicine, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland. Telephone: 41-21-31-44-373; Fax: 41-21-31-44-349; e-mail: Franz.Buchegger{at}CHUV.CH

Received January 25, 2008; accepted for publication April 23, 2008.

Disclosure: A.B.D. has acted as a consultant for Bayer Schering (Zevalin®). No other potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.

Advanced-stage follicular lymphoma is incurable by conventional treatment. Rituximab has been introduced in various combinations with chemotherapy and has resulted in a significantly superior treatment outcome compared with chemotherapy alone. Multiple studies have also shown the efficacy of radioimmunotherapy (RIT) both as a single agent and in combination with chemotherapy. Rituximab and RIT have clearly distinct mechanisms of action, the first acting exclusively as a biological treatment, while the second acts by a combination of biologic mechanisms and radiation effects. Despite the therapeutic efficacy of both approaches, the potential exists to further improve both modalities. Repeat administrations of RIT using appropriate radioisotopes for treatment of residual disease or new targeting strategies might afford additional benefits. Unlabeled antibody treatment could potentially benefit from the combination of antibodies directed against different target antigens or combination therapy with cytokines capable of further mobilizing patients' cellular defenses. In this review, we hypothesize that the combination of an optimized biological treatment together with radiolabeled antibodies and chemotherapy early in the disease course of advanced-stage follicular lymphoma may represent the best approach to achieve prolonged disease-free survival and eventually cure.

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