Rituximab (Rituxan) is the first monoclonal antibody (MoAb) approved
for the treatment of non-Hodgkins lymphoma (NHL). This
anti-CD20 MoAb is effective in inducing apoptosis,
complement-dependent cytotoxicity (CDC), and antibody-dependent
cellular cytotoxicity (ADCC). In single-agent studies in relapsed or
refractory low-grade or follicular NHL (International Working Formula
[IWF] types A-D), an overall response rate (ORR) of 48% has been reported.
In this phase II trial, 31 patients (requiring treatment for
progressive disease) with bulky low-grade or follicular NHL (³
1 lesion ³ 10 cm) received rituximab
at 375 mg/m² weekly × 4 infusions. Patient characteristics
included: 52% male; median age, 55 years; median 4 years from
diagnosis; and median three prior therapies.
Most related adverse events were mild to moderate (usually first
infusionrelated): fever (61%), chills (36%), leukopenia (23%),
nausea (19%), dizziness (19%), and throat irritation (19% of
patients). Tumor lysis syndrome was not reported. Four patients had
grade 3 or 4 nonhematologic adverse events: pulmonary (two patients),
chills (one patient), and hypotension (one patient). One patient died
with bronchiolitis obliterans 10 months posttreatment. Seven patients
had a transient grade 3 or 4 hematologic adverse event: hemoglobin
(three patients), absolute neutrophil count (ANC; six patients), and
ANC + platelets (one patient). No patient developed a human
antichimeric antibody (HACA) reaction. There were no grade 3 or 4 infections.
In evaluable patients, the ORR was 43% (12/28) with 1 complete
response (CR) and 11 partial responses (PRs). The median time to
progression (responders) was 8.1 months, with a median duration of
response of 5.9 months. Of 12 responses, 3 are ongoing, with a
maximum time to progression of 24.6+ months. B-symptoms resolved in
Exploratory analysis of prognostic factors revealed: 55% ORR in
patients with IWF types B, C, D (12/22); higher MoAb levels in
responders; and no correlation with number of relapses, number of
prior chemotherapies, or chemoresistance.
CONCLUSION: Bulky disease is associated with poor prognosis in
patients treated with chemotherapy (poor response, treatment-related
mortality, short survival). Outpatient therapy (four infusions in 22
days) with rituximab is safe and effective in bulky low-grade or
follicular NHL and does not limit subsequent treatment options.