Rituximab in Combination With Fludarabine Chemotherapy in Low-Grade or Follicular Lymphoma

Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 03/2005; 23(4):694-704. DOI: 10.1200/JCO.2005.02.172
Source: PubMed


To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma.
This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks.
An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal.
Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

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    • "fludarabine, are powerful therapeutic agents in several lymphoproliferative diseases. Remission of CAD following fludarabine monotherapy has been reported in two patients (Jacobs, 1996; Berentsen et al, 2006), and the fludarabine-rituximab combination has yielded high response rates in WM (Treon et al, 2009) and other low-grade non-Hodgkin lymphoma (Czuczman et al, 2005). "
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    ABSTRACT: Primary chronic cold agglutinin disease (CAD) is a clonal lymphoproliferative disorder accounting for 13-15% of autoimmune haemolytic anaemias. Significant advances have been made in treatment, which was largely unsuccessful until recently. The essential clinical, immunological and pathological features are reviewed, focusing on their relevance for therapy. Non-pharmacological management still seems sufficient in some patients. With the recent improvements, however, drug therapy seems indicated more often than previously thought. Corticosteroids should not be used to treat CAD. Half of the patients respond to rituximab monotherapy; median response duration is 11 months. Fludarabine-rituximab combination therapy is very effective, resulting in 75% response rate, complete remissions in about 20%, and more than 66 months estimated response duration. Toxicity is a concern, and benefits should be carefully weighed against risks. An individualized approach is discussed regarding the choice of fludarabine-rituximab combination versus rituximab monotherapy. Patients requiring treatment should be considered for prospective trials.
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