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Monoclonal Antibodies in Hematologic Malignancies: Research and Clinical Developments

Monoclonal Antibodies in Hematologic Malignancies: Research and Clinical Developments

It is amazing how, over the past 5 years, the world of clinical research in the lymphoid malignancies has been totally redirected by one molecule called rituximab (Rituxan). Since its approval by the US Food and Drug Administration for the treatment of relapsed and refractory follicular and low-grade B-cell non-Hodgkin’s lymphoma (NHL), the use of this monoclonal antibody has become so ubiquitous that it has earned the nickname "vitamin R." Those who attended the 43rd Annual Meeting of the American Society of Hematology could not help but be overwhelmed by the number of abstracts discussing not only rituximab (more than 108), but also other new and exciting antibodies and radioimmunoconjugates, such as alemtuzumab (Campath), epratuzumab (hLL2 [LymphoCide]), yttrium-90 ibritumomab tiuxetan (Zevalin), and tositumomab/iodine-131 tositumomab (Bexxar).

At no time in recent memory has so much enthusiasm been generated for new therapies in the treatment of patients with lymphoid malignancies. These new antibodies and radioimmunoconjugates have irreversibly changed our treatment paradigms. Clearly, it is becoming increasingly difficult to conduct a clinical trial in patients with NHL that either does not incorporate rituximab or excludes patients who received prior rituximab therapy.

However, high expectations must be tempered with attention to data. We must learn to separate the science from the religion, the facts from the opinions (Cheson: N Engl J Med 346:280-282, 2002). Although a drug such as rituximab has a favorable toxicity profile, excessive use/abuse may lead to unexpected complications from chronic B-cell depletion. Inappropriate selection of patients for radioimmunoconjugate therapy, such as those with greater than 25% bone marrow involvement, decreased stem cell reserves, or a preexisting cytogenetic abnormality, may lead to profound and prolonged cytopenias or myelodysplastic syndrome/acute myelogenous leukemia. Nevertheless, these agents offer a major advance over our current therapies. The possibility of moving away from nonspecific cytotoxic therapy to less toxic targeted treatments is extremely attractive and may hopefully lead to improved outcomes for patients with lymphoid malignancies.

We are clearly in the midst of a rapid and dramatic change in the treatment paradigms for patients with NHL, as well as other malignant and benign hematologic disorders. The abstracts reviewed in this supplement illustrate that clinical research in lymphoid malignancies has come a long way in a short time, but that a lot of work remains to be done.

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