Rituximab: First Report of a Phase II Trial in NHL Patients With Bulky Disease

Rituximab (Rituxan) is the first monoclonal antibody (MoAb) approved for the treatment of non-Hodgkin’s 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 infusion–related): 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 8/10 patients.

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.

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