Rituximab: a review of its use in chronic lymphocytic leukaemia, low-grade or follicular lymphoma and diffuse large B-cell lymphoma.
ABSTRACT Rituximab (MabThera, Rituxan) is a chimeric mouse anti-human CD20 monoclonal antibody. This article reviews the use of intravenous rituximab in the treatment of chronic lymphocytic leukaemia (CLL), low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. The addition of rituximab to fludarabine plus cyclophosphamide significantly prolonged progression-free survival both in previously untreated patients with CLL and in those with relapsed or refractory CLL, according to the results of two randomized, open-label, multicentre trials. In patients with previously untreated advanced follicular lymphoma, the addition of rituximab to chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone [CHOP], cyclophosphamide, vincristine and prednisone [CVP], mitoxantrone, chlorambucil and prednisolone, or cyclophosphamide, doxorubicin, etoposide and prednisolone) was generally associated with better outcomes than chemotherapy alone in randomized, multicentre trials. In a similarly designed trial, progression-free survival was significantly longer in previously untreated patients with follicular lymphoma, other indolent lymphomas or mantle-cell lymphoma who received rituximab plus bendamustine than in those receiving rituximab plus CHOP. Monotherapy with rituximab also demonstrated efficacy in patients with relapsed or refractory low-grade or follicular lymphoma, according to the results of noncomparative trials. In terms of maintenance therapy, progression-free survival was significantly prolonged with rituximab maintenance therapy versus observation alone in patients with advanced indolent lymphoma who had not progressed following first-line therapy with CVP and in patients with relapsed or refractory follicular lymphoma who had responded to CHOP (with or without rituximab), according to the results of randomized, open-label, multicentre trials. In four randomized, open-label, multicentre trials in younger or elderly patients with previously untreated diffuse large B-cell lymphoma, event-free survival, failure-free survival, progression-free survival and overall survival were generally improved to a significant extent by the addition of rituximab to CHOP or CHOP-like chemotherapy. Intravenous rituximab was generally well tolerated in patients with CLL, low-grade or follicular lymphoma, or diffuse large B-cell lymphoma, both as monotherapy and when administered in combination with chemotherapy. Infusion reactions were one of the most commonly occurring adverse events in patients receiving intravenous rituximab. The results of pharmacoeconomic modelling analyses demonstrated that rituximab appears to be cost effective in patients with previously untreated follicular lymphoma, in patients with follicular lymphoma receiving rituximab maintenance therapy following treatment for relapsed or refractory disease and in patients with previously untreated diffuse large B-cell lymphoma. In conclusion, rituximab remains a valuable therapy in patients with CLL, low-grade or follicular lymphoma and diffuse large B-cell lymphoma and, in a variety of treatment settings, represents the standard of care.
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ABSTRACT: Antibodies are well established in mainstream clinical practice and present an exciting area for collaborative research and development in industry and academia alike. In this review, we will provide an overview of the current market and an outlook to 2015, focussing on whole antibody molecules while acknowledging the next generation scaffolds containing variable fragments. The market will be discussed in the context of disease targets, particularly in the areas of oncology and immune disorders which generate the greatest revenue by a wide margin. Emerging targets include central nervous system disorders which will also stimulate new delivery strategies. It is becoming increasingly apparent that a better understanding of bioprocessing is required in order to optimize the steps involved in the preparation of a protein prior to formulation. The latter is outside the scope of this review and nor is it our intention to discuss protein delivery and pharmacokinetics. The challenges that lie ahead include the discovery of new disease targets and the development of robust bioprocessing operations.International Journal of Pharmaceutics 12/2011; 440(1). DOI:10.1016/j.ijpharm.2011.12.039 · 3.79 Impact Factor
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ABSTRACT: Human cluster of differentiation (CD) antigen 19 is a B cell-specific surface antigen and an attractive target for therapeutic monoclonal antibody (mAb) approaches to treat malignancies of B cell origin. MEDI-551 is an affinity-optimized and afucosylated CD19 mAb with enhanced antibody-dependent cellular cytotoxicity (ADCC). The results from in vitro ADCC assays with Natural Killer cells as effector cells, demonstrate that MEDI-551 is effective at lower mAb doses than rituximab with multiple cell lines as well as primary chronic lymphocytic leukaemia and acute lymphoblastic leukaemia samples. Targeting CD19 with MEDI-551 was also effective in several severe combined immunodeficiency lymphoma models. Furthermore, the combination of MEDI-551 with rituximab resulted in prolonged suppression of tumour growth, demonstrating that therapeutic mAbs with overlapping effector function can be combined for greater tumour growth inhibition. Together, the data demonstrate that MEDI-551 has potent antitumour activity in preclinical models of B cell malignancies. The results also suggest that the combination of the ADCC-enhanced CD19 mAb with an anti-CD20 mAb could be a novel approach for the treatment of B cell lymphomas.British Journal of Haematology 09/2011; 155(4):426-37. DOI:10.1111/j.1365-2141.2011.08857.x · 4.96 Impact Factor
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ABSTRACT: The impact on health related quality of life (HRQoL) of rituximab maintenance (R-M) versus observation (OBS) after induction for treatment of follicular lymphoma (FL) is unclear. We reviewed the charts of 137 patients (53% female, 87% White, age 61.0 ± 12.4 years) who received either R-M (n = 53) or OBS (n = 84) after chemotherapy induction for newly diagnosed FL at community oncology practices within the US. Patients (65% with advanced disease; 48% with a high FLIPI score [3-5]) had completed ≥1 Patient Care Monitor HRQoL survey in the period following front-line therapy, and were excluded if they had progressed during front-line therapy. Linear mixed models showed that postinduction, most symptoms were stable, with patients on R-M reporting HRQoL that was equal to that reported by OBS patients. Among R-M patients, receipt of rituximab was associated with improved psychological symptoms.06/2011; 2(3):129-39. DOI:10.1177/2040620711407675