Toxicity and Efficacy of the Anti-CD20 Antibody Rituximab (Rituxan) in Patients With B-Cell Chronic Lymphocytic Leukemia: A Phase I/II Study

Low toxicity and high efficacy have been observed after treatment of patients with relapsed low-grade follicular non-Hodgkin’s lymphoma (NHL) using the chimeric monoclonal anti-CD20 antibody rituximab (Rituxan). Since the CD20-antigen is also expressed on circulating tumor cells in chronic lymphocytic leukemia (CLL), we treated 12 patients with fludarabine (Fludara)-resistant CLL or leukemic variants of other low-grade NHLs with 375 mg/m² of rituximab once weekly for 4 weeks.

Median age of patients was 58 years (range, 26 to 79 years). All patients were in a second or higher relapse and had received a median of three prior chemotherapeutic regimens (range, two to five). Peripheral lymphocyte counts at baseline varied from 0.2 × 10⁹/L to 294.3 ×10⁹/L. During the first antibody infusion, patients with lymphocyte counts exceeding 50.0 ×10⁹/L experienced a severe cytokine release syndrome (Blood 94:2217-2224, 1999). At 90 minutes after onset of the infusion, mean serum levels of tumor necrosis factor–alpha (TNF-alpha) and interleukin-6 (IL-6) peaked at 500 pg/mL (baseline, 20 pg/mL) and 280 pg/mL (baseline, 25 pg/mL), respectively. Serum interferon-gamma (IFN-gamma) concentrations were not elevated.

Serious side effects, eg, dyspnea or hypotension, were most likely due to leukostasis of the circulating tumor cells in the lung and other organs. The frequency and severity of adverse events during the first rituximab infusion were significantly less pronounced in patients with less than 50.0× 10⁹/L peripheral lymphocytes (P = .009). First-dose toxicity was also reduced by the use of a modified stepped-up infusion schedule.

Although one patient with the leukemic variant of a mantle cell NHL is in continuous complete remission 19 months after treatment with 4 × 375 mg/m² of rituximab, response rates in evaluable patients with relapsed CLL were modest. There was one complete response (CR; duration, 9 weeks), one partial response (PR; duration, > 22 weeks), seven cases of stable disease (SD), and one case of progressive disease (PD).

CONCLUSION: Further clinical studies in patients with CLL are necessary to evaluate the toxicity and efficacy of higher doses of rituximab administered over a longer period of time, as wel

Click here for Dr. Bruce Cheson’s commentary on this abstract.