New Treatment Approaches To Indolent Non-Hodgkin’s Lymphoma

https://doi.org/10.1053/j.seminoncol.2003.12.007Get rights and content

Abstract

Disseminated indolent non-Hodgkin’s lymphoma (NHL) is considered incurable with conventional chemotherapy regimens, and more than 50% of patients die within 5 years of their first relapse. Therefore, newer treatment approaches have been used to try to improve survival and ultimately provide a cure for patients with disseminated indolent NHL. The anti-CD20 monoclonal antibody rituximab has been extensively evaluated and is now an integral component of many treatment strategies. The activity of rituximab was first shown in the pivotal trial in patients with relapsed and refractory low-grade and follicular lymphoma. More recent studies have shown somewhat higher activity of rituximab when used first-line, with further improvements with maintenance therapy. Rituximab in combination with chemotherapy has been shown to achieve high response rates, and two prospective randomized studies from the German Low-grade Lymphoma Study Group have shown significantly higher response rates and longer survival for patients receiving rituximab concurrently with chemotherapy compared with those receiving chemotherapy alone. Further data from ongoing phase III studies are still needed to determine whether rituximab can help alter the natural history of indolent NHL, and longer follow-up of these patients will help determine the optimal role for rituximab in treatment of indolent NHL.

Section snippets

Single-agent rituximab in indolent non-hodgkin’s lymphoma

The single-agent activity of rituximab in indolent NHL was shown in the pivotal trial in patients with relapsed and refractory low-grade and follicular lymphoma.2 An overall response rate of 48% was observed, with a median response duration of 13 months. In a separate study of 31 patients with bulky disease who were excluded from the pivotal trial, a response rate of 43% was obtained, with a median time to progression of 8.1 months.3 The efficacy of rituximab in this setting is thus broadly

First-line sstudies of rrituximab monotherapy

Two studies evaluating first-line use of the standard weekly-×-4 schedule of rituximab monotherapy in patients with asymptomatic or low tumor burden stage III/IV follicular NHL have been conducted,6, 7 as well as other studies in patients with symptomatic disease in which first-line monotherapy was followed by consolidation or maintenance treatment with rituximab8, 9 or interferon-α2a.10 The efficacy of first-line rituximab in these settings is summarized in Table 1.

In a French study, 50

Combination therapy in indolent non-hodgkin’s lymphoma

Rituximab kills CD20+ cells through multiple mechanisms, including complement-mediated cytotoxicity, antibody-dependent cellular cytotoxicity, and induction of apoptosis.12, 13, 14 Rituximab has also been shown to sensitize resistant cell lines to chemotherapy in vitro.15, 16 These factors combined with minimal overlapping toxicity provide the rationale for combining rituximab with chemotherapy agents.

The efficacy and safety of rituximab in combination with CHOP (cyclophosphamide, doxorubicin,

Conclusions

Rituximab has been used in a wide range of combinations and settings in patients with indolent NHL with the goal of improving outcome compared with standard chemotherapy with encouraging results. First-line rituximab monotherapy achieves high response rates. A range of immunochemotherapy regimens have achieved response rates approaching 100%, with high complete response rates and very promising durable response durations, and the use of maintenance rituximab is being explored following

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    Dr Seymour has received honoraria from Roche Pharmaceuticals and Schering AG.

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