We know that cell death can occur through complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and (in some experimental systems) direct signaling. With regard to mechanism, we know that rituximab binds to the large extracellular loop of CD20 on the surface of B-cells and depletes them. In addition to rituximab’s safety profile, uncertainties about its mechanism of action, controversies about optimal dosing, and unique and still only partially appreciated aspects of its pharmacokinetics add to the “magic”. –In this regard we may in fact have been spoiled and other monoclonal antibodies or targeted agents may not necessarily be so safe and unproblematic to integrate into existing treatment regimens. Who would have ever thought that a drug which essentially obliterates an entire arm of the immune system for extended periods of time, could be as safe as rituximab has proven to be? Furthermore, rituximab can be combined with virtually any existing treatment strategy without significantly increased toxicity. First of all, there is the experience that it can be safely added to virtually any treatment. In fact, rituximab has demonstrated safety and activity in so many diseases that it has been nicknamed “vitamin R”! All joking aside, as much as the use of rituximab has enhanced treatment options, there are still many unanswered questions and opportunities for further improvement remain aplenty.ĭespite a decade of experience, rituximab has preserved a certain “magical” quality. Rituximab has also demonstrated considerable utility in a number of autoimmune hematologic and rheumatologic diseases, and is increasingly being turned to as a well-tolerated, relatively safe, and often less invasive alternative to traditional therapies for these conditions. Both as a single agent and in combination with cytotoxic chemotherapy, rituximab has significantly improved response rates and progression-free survival in a variety of lymphoid malignancies, as well as overall survival and cure rates in aggressive NHL. Over a decade later, rituximab has become one of the biggest therapeutic advancements in the treatment of lymphoid malignancies, redefining the standard of care for a vast majority of B-cell neoplasms. On November 26 th, 1997, a little-known monoclonal antibody called rituximab was approved by the US Food and Drug Administration for the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL).
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