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Rituximab

A Review of its Use in Chronic Lymphocytic Leukaemia, Low-Grade or Follicular Lymphoma and Diffuse Large B-Cell Lymphoma

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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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    Gillian M. Keating

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Correspondence to Gillian M. Keating.

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Various sections of the manuscript reviewed by: K.A. Foon, Department of Hematological Malignancie, Nevada Cancer Institute, Las Vegas, Nevada, USA; C. Gisselbrecht, Hôpital Saint-Louis, Hémato-oncologie, Paris, France; G. Hess, Department of Haematology/Oncology, Johannes Gutenberg-University, Mainz, Germany; M. Herold, HELIOS Klinikum Erfurt GmbH, 4. Medizinische Klinik, Erfurt, Germany; T. Robak, Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.

Data Selection

Sources: Medical literature published in any language since 1980 on rituximab, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘rituximab’ or ‘MabThera’ or ‘monoclonal-antibody-IDEC-C2B8’ and ‘non-Hodgkin’s lymphoma’ or ‘lymphoma non-Hodgkins’ or ‘chronic lymphocytic leukaemia’ or ‘chronic lymphatic leukaemia’. Searches were last updated 22 June 2010.

Selection: Studies in patients with chronic lymphocytic leukaemia, low-grade or follicular lymphoma or diffuse large B-cell lymphoma who received rituximab. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Rituximab, chronic lymphocytic leukaemia, non-Hodgkin’s lymphoma, follicular lymphoma, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability, pharmacoeconomics.

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Keating, G.M. Rituximab. Drugs 70, 1445–1476 (2010). https://doi.org/10.2165/11201110-000000000-00000

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