Background and Objectives. To determine the clinical activity and safety of the combination immunotherapy of the chimeric anti-CD20 antibody, rituximab, and interferon (IFN)-α2a. Design and Methods. Sixty-four patients with relapsed low-grade or follicular B-cell non-Hodgkin’s lymphoma received 4 infusions of rituximab (375 mg/m2 per infusion) after priming and simultaneous treatment with IFN-α2a. Results. The overall response rate was 70% with 33% complete responses. The median duration of response is 19 months, after a median follow-up of 22 months. By univariate analysis none of the most common prognostic factors predicted for response to therapy. After treatment 10 patients became bcl2 negative in the bone marrow, but no correlation between molecular and clinical response was found. Fifty-three patients (83%) had adverse events that were drug related or of unknown origin. The number of adverse events per patient varied from 1 to 21. Considering all 272 events, 231 (85%) were grade 1 or 2, 36 (13%) grade 3 and 5 (2%) grade 4. Twenty-three patients required a reduction in the dose and/or short discontinuation of IFN treatment, either during priming or subsequent treatment. The most frequent adverse events were leukopenia, fever, neutropenia, hypotension and thrombocytopenia. Interpretation and Conclusions. This report shows that combination immunotherapy (rituximab + IFNα2a) is active and relatively well tolerated. The over all response rate of 70% and the median duration
of remission of 19 months compare favorably with
the results obtained with rituximab alone in a similar subset of patients. Randomized trials investigating rituximab versus combination immunotherapy
are needed.