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Single-Agent Rituximab in Early-Stage Chronic Lymphocytic Leukemia

Single-Agent Rituximab in Early-Stage Chronic Lymphocytic Leukemia

Currently, patients with early-stage chronic lymphocytic leukemia (CLL) without active disease are observed. However, those patients with elevated beta-2-microglobulin levels appear to have a shorter median survival (6 years vs 10+ years). Strategies designed to impact the eventual progression of disease include use of targeted therapies with minimal long-term risk. Single-agent rituximab (Rituxan) has activity in previously treated CLL (J Clin Oncol 19:2165, 2001; 19:2153, 2001) and in untreated low-grade lymphomas (Semin Oncol 27:25, 2000). We designed this study to investigate the activity of rituximab in untreated high-risk, early-stage CLL.

Patients were eligible if they had untreated Rai stage 0 to II CLL with beta-2-microglobulin levels ³ 2.0 mg/dL, without indications for therapy according to the National Cancer Institute Working Group criteria. Rituximab was given at 375 mg/m² weekly for 8 weeks. Baseline cytokine profiles known to be prognostic in CLL, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha (Blood 97:256, 2001), were obtained with serial measurements when feasible. Thirty-one patients have been enrolled to date; characteristics are as follows: median age, 67 years (range: 50-82 years); Rai stage II in 32%; and median beta-2-microglobulin level, 3.6 mg/dL.

The overall response rate in 21 evaluable patients (eight under active therapy, two not reassessed) was 90% (19% complete response, 19% nodular partial response, 48% partial response). Significant reductions in fatigue were reported. Two patients did not respond. With a median follow-up of 8 months (range: 2-16 months), one patient with partial response progressed.

No unexpected toxicities were observed; most were grade 1/2 fever, chills, and/or hypotension related to the first infusion. Samples were collected for cytokine analysis in 10 patients to date. Although the numbers were small, preliminary observations suggested reductions in TNF-alpha levels correlated with response.

CONCLUSION: Rituximab has significant activity in early-stage CLL. Impact on survival and time to progression requires longer follow-up. Further investigation of the effect of rituximab on cytokine profiles and implementation of strategies to modulate CD20 expression is planned.

Click here to read Dr. Bruce Cheson's commentary on this abstract.

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