Interferon alfa for the treatment of follicular lymphomas

Recombinant human interferon alfa (rIFN-alpha) has demonstrated significant activity against follicular lymphomas when applied as salvage treatment after the failure of conventional therapy. It has also been shown to exhibit synergistic antitumor activity when given simultaneously with certain cytostatic agents.

Against this background, two major strategies were followed to incorporate rIFN-alpha into the first-line treatment of follicular lymphomas: application simultaneously with initial cytotoxic chemotherapy and application as maintenance treatment after successful initial chemotherapy.

Of the five prospective randomized trials performed to assess the activity of rIFN-alpha in combination with initial chemotherapy versus the activity of chemotherapy alone, three studies showed that rIFN-alpha plus chemotherapy yielded no beneficial effect on remission rate, remission duration, or overall survival. In all three of these trials, chemotherapy consisted of a single alkylating agent. In contrast, a significant improvement in remission rate and remission duration was observed in two studies when rIFN-alpha was combined with anthracycline-containing regimens. Five prospective randomized studies have evaluated the role of rIFN-alpha as maintenance therapy after successful cytoreductive chemotherapy. Four of these studies have either found no significant prolongation of the disease-free interval or shown significant improvement in disease-free survival only in patients achieving a complete remission with initial cytoreductive treatment. In all four studies, relatively low doses of rIFN-alpha were administered for a limited time. A different outcome emerged in the fifth study, by the German Low Grade Lymphoma Study Group, in which patients received higher doses of rIFN-alpha with no restriction on duration of therapy. Patients treated with rIFN-alpha had a significantly prolonged median progression-free interval (30 versus 19 months), and at 4 years, 45% of patients receiving rIFN-alpha maintenance therapy remained relapse-free, compared with 26% of patients in the untreated control group (P = 0.003).

Collectively, these data demonstrate that rIFN-alpha adds substantially to the treatment of follicular lymphomas either when combined with anthracycline-containing cytoreductive chemotherapy or when given as long-term maintenance therapy.