Monoclonal Antibodies: A New Era in the Treatment of Non-Hodgkin's Lymphoma

Authors: Grillo-Lopez A.J.; Dallaire B.K.; McClure A.; Weaver R.; Varns C.; Wei A.; Allen R.; Lee D.; Shen D.; Leonard J.; Multani P.; White C.A.

Source: Current Pharmaceutical Biotechnology, Volume 2, Number 4, December 2001 , pp. 301-311(12)

Publisher: Bentham Science Publishers

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Abstract:

Monoclonal antibodies (MAbs) have been used as therapeutic agents for many years. In 1997, Rituxan (IDEC-C2B8, rituximab, MabThera) became the first MAb to be approved by the FDA for a cancer indication. Rituxan served to heighten interest in the therapeutic applications of MAbs. Herceptin (for patients with breast cancer) and Mylotarg (for patients with acute myeloid leukemia) were approved shortly thereafter. Literally dozens of antibodies are currently under investigation for a variety of malignant and non-neoplastic indications. Rituxan is effective in patients with low-grade or follicular, relapsed or refractory non-Hodgkin's lymphoma (NHL). The response rate and time to progression (responders) are in the 50percent and 13 months range, respectively. It is also active in intermediate-grade NHL where a large randomized study, in combination with CHOP chemotherapy, has shown a statistically significant increase in complete response (CR) rate (75percent vs. 60percent), prolongation of 1 year event-free survival (69percent vs. 49percent) and of overall survival (83percent vs. 68percent) as compared to CHOP alone. This marks the first time that any agent has shown results superior to CHOP, the curative gold standard for this type of NHL. Other promising antibodies under clinical investigation include: Hu1D10; Anti CD19, 22, 52, and anti-Id antibodies. The safety profile, clinical activity, and mechanism of action of these MAbs make them ideal candidates for combination with chemotherapy or biologicals. Over the next few years, we will see very significant therapeutic advances emerge as this important research yields additional clinical results.

Keywords: Monoclonal Antibodies; Efficacy-Limiting Factors; Anti-Idiotype Antibodies; Efficacy-Limiting Factors; MAb therapy; Rituximab Eight-Infusion Study; Complement-dependent cytotoxicity; Event-free survival

Language: English

Document Type: Review article

DOI: 10.2174/1389201013378563

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