Interferon-alfa Added to COPA Improves Survival in NHL Patients

MADISON, Wisconsin—The addition of interferon-alfa to the COPA regimen (cyclophosphamide, 600 mg/m²; vincristine, 1.2 mg/m²; prednisone, 100 mg; and doxorubicin, 50 mg/m²) improves survival in patients with clinically aggressive low- and intermediate-grade non-Hodgkin’s lymphoma (NHL), Richard Smalley, MD, of Synertron, Inc., said at the American Society of Hematology meeting. He presented 10-year follow-up results of an ECOG trial begun in 1986.

Patients with stage III or IV disease, IWF (International Working Formulation) groups C, D, and E, and bulky or symptomatic IWF groups A or B non-Hodgkin’s lymphoma all received a cycle of COPA every 28 days for 8 to 10 cycles. The 291 patients were then randomized to receive interferon-alfa, 6 MU/m² on days 22 to 26 of each cycle or no other therapy.

“Patients who responded or were stable were followed every 2 to 4 months for relapse and annually for survival,” Dr. Smalley said. There were some dose de-escalations of the cyclophosphamide and doxorubicin because of myelosuppression. Everyone on the study received the full dose of prednisone and interferon-alfa. “The interferon-alfa toxicity was minimal and acceptable,” he said.

Previous reports showed an overall response rate of 86% in both treatment groups (COPA vs I-COPA). The current analysis shows that the addition of interferon-alfa induced a prolonged time to treatment failure, with a median of 1.9 years for the COPA group and 2.9 years for the I-COPA group (P = .008). Survival was also better in the I-COPA group; 7.9 years vs 5.7 years with COPA alone (P = .04).

Subset analyses showed a trend for increased survival with interferon-alfa for both intermediatedisease and low-grade disease, but the differences did not reach statistical significance.

There was a significant difference in time to treatment failure favoring the interferon-alfa arm in patients with low-grade lymphoma (IWF A, B, C) (P = .005) and in those with follicular lymphoma (IWF B, C, D) (P = .009).

From this analysis, Dr. Smalley said, it seems that interferon-alfa when added to COPA improves survival in patients with clinically aggressive low-grade NHL and in D and E intermediate-grade NHL. “My conclusion is that if you’re using a doxorubicin-type regimen, interferon-alfa does improve survival,” he said.