Article

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

ABSTRACT 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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    British Journal of Haematology 03/2011; 153(3):309-17. DOI:10.1111/j.1365-2141.2011.08643.x · 4.96 Impact Factor
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    • "This potentiation of granulocytopenia may be related more to an undetermined interaction of rituximab with fludarabine than with bortezomib given the similar myelosuppression between dose levels 5a and 5b. However, it is possible that rituximab may have potentiated bortezomib-related thrombocytopenia, a common toxicity of the proteasome inhibitor that has not been otherwise observed with only fludarabine and rituximab (Czuczman, et al 2005). However, further investigation to validate these observations is needed given the small numbers treated at each dose level. "
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    • "Of particular concern, however, was the occurrence in this study of delayed neutropenia several months after completion of therapy, which led directly to two infectious deaths. Although grade 3–4 neutropenia is commonly seen during therapy, neutropenia occurring outside the usual post-therapy window but earlier than expected for secondary myelodysplasia has not been reported in prior studies of FR (Byrd, et al 2003, Czuczman, et al 2005, Savage, et al 2003, Schulz, et al 2002) or in long-term follow-up studies of the rate of secondary myelodysplasia and AML (Cheson, et al 1999b, McLaughlin, et al 2005, Morrison, et al 2002). Both of these patients had aplastic bone marrow affecting all lineages but without evidence of cytogenetic abnormalities associated with MDS. "
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