Maria Jesús Blanco | University of Salamanca (original) (raw)

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illness, new treatments are needed to prolong survival, with the ultimate goal to provide cure. F... more illness, new treatments are needed to prolong survival, with the ultimate goal to provide cure. For patients with aggressive lymphoma, unmet needs include higher initial cure rates, improved salvage chemotherapy options, and less toxic therapies for old and frail patients. Conventional methods of treatment, including chemother-apy and radiation, are associated with toxicity and lack specific antitumor-targeted activity. Cell–surface proteins, such as CD19, CD20, and CD22, are highly expressed on B-cell lym-phomas and represent key potential targets for treatment. Antibody therapy directed against CD20 has had the most important clinical impact to date. CD20 is thought to be involved in the regulation of intracellular calcium, cell cycle, and apoptosis. CD20 is not shed, modulated, or in ternalized significantly upon antibody binding, thus making it an ideal target for passive immunotherapy. 5 Over the past two decades, significant progress has been made in the development of new therapies for B-cell lym-phoma. Perhaps the most important advance is the addition of rituximab (Rituxan, Genentech/Biogen Idec), which the FDA approved for use in the U.S. in 1997. Rituximab is a chimeric (mouse and human) monoclonal antibody directed against the B-cell antigen CD20. It depletes B cells by several mechanisms , including direct antibody-dependent cellular cytotoxi-city (ADCC), complement-mediated cell death, and signaling apoptosis. 6–11 Phase 1 trials of two doses of rituximab (500 mg/m 2 and 375 mg/m 2 for four weeks) showed clinical responses with no dose-limiting toxicity. 12 The weekly 375-mg/m 2 dose, given for four weeks, was selected for further phase 2 evaluation and is currently the standard single-agent dose and schedule. Since this first reported activity, the role of rituximab has expanded to include both indolent and aggressive lymphomas. This article addresses the effect of rituximab on survival and long-term outcomes in patients with NHL. TREATMENT Indolent, Low-Grade Lymphomas Unlike aggressive lymphomas, indolent B-cell lymphomas are not considered curable with conventional therapies. Many patients are observed for prolonged periods without requiring treatment. 13 In one study, more than 50% of the patients remained untreated for a median period of almost six years after diagnosis. 14 Treatment goals focus on maintaining good quality of life with minimal symptoms. The indications for treatment include the presence of B symptoms (fevers, night sweats, and weight loss), compromise of normal organ func-ABSTRACT Non-Hodgkin's lymphoma (NHL) is the most common hematological malignancy in adults, with B-cell lymphomas accounting for 85% of all NHLs. The most substantial advancement in the treatment of B-cell malignancies, since the advent of combination chemotherapy, has been the addition of the monoclonal anti-CD20 antibody rituximab (Rituxan). Since its initially reported single-agent activity in indolent lymphomas in 1997, the role of rituximab has expanded to cover both indolent and aggressive lymphomas. This article focuses on the impact of rituximab on the treatment , survival, and long-term outcomes of patients with indolent and aggressive lymphomas over the past two decades.

illness, new treatments are needed to prolong survival, with the ultimate goal to provide cure. F... more illness, new treatments are needed to prolong survival, with the ultimate goal to provide cure. For patients with aggressive lymphoma, unmet needs include higher initial cure rates, improved salvage chemotherapy options, and less toxic therapies for old and frail patients. Conventional methods of treatment, including chemother-apy and radiation, are associated with toxicity and lack specific antitumor-targeted activity. Cell–surface proteins, such as CD19, CD20, and CD22, are highly expressed on B-cell lym-phomas and represent key potential targets for treatment. Antibody therapy directed against CD20 has had the most important clinical impact to date. CD20 is thought to be involved in the regulation of intracellular calcium, cell cycle, and apoptosis. CD20 is not shed, modulated, or in ternalized significantly upon antibody binding, thus making it an ideal target for passive immunotherapy. 5 Over the past two decades, significant progress has been made in the development of new therapies for B-cell lym-phoma. Perhaps the most important advance is the addition of rituximab (Rituxan, Genentech/Biogen Idec), which the FDA approved for use in the U.S. in 1997. Rituximab is a chimeric (mouse and human) monoclonal antibody directed against the B-cell antigen CD20. It depletes B cells by several mechanisms , including direct antibody-dependent cellular cytotoxi-city (ADCC), complement-mediated cell death, and signaling apoptosis. 6–11 Phase 1 trials of two doses of rituximab (500 mg/m 2 and 375 mg/m 2 for four weeks) showed clinical responses with no dose-limiting toxicity. 12 The weekly 375-mg/m 2 dose, given for four weeks, was selected for further phase 2 evaluation and is currently the standard single-agent dose and schedule. Since this first reported activity, the role of rituximab has expanded to include both indolent and aggressive lymphomas. This article addresses the effect of rituximab on survival and long-term outcomes in patients with NHL. TREATMENT Indolent, Low-Grade Lymphomas Unlike aggressive lymphomas, indolent B-cell lymphomas are not considered curable with conventional therapies. Many patients are observed for prolonged periods without requiring treatment. 13 In one study, more than 50% of the patients remained untreated for a median period of almost six years after diagnosis. 14 Treatment goals focus on maintaining good quality of life with minimal symptoms. The indications for treatment include the presence of B symptoms (fevers, night sweats, and weight loss), compromise of normal organ func-ABSTRACT Non-Hodgkin's lymphoma (NHL) is the most common hematological malignancy in adults, with B-cell lymphomas accounting for 85% of all NHLs. The most substantial advancement in the treatment of B-cell malignancies, since the advent of combination chemotherapy, has been the addition of the monoclonal anti-CD20 antibody rituximab (Rituxan). Since its initially reported single-agent activity in indolent lymphomas in 1997, the role of rituximab has expanded to cover both indolent and aggressive lymphomas. This article focuses on the impact of rituximab on the treatment , survival, and long-term outcomes of patients with indolent and aggressive lymphomas over the past two decades.