Low toxicity and high efficacy have been
observed after treatment of patients with relapsed low-grade
follicular non-Hodgkins 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 factoralpha (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