Long-Term Follow-Up of the Italian Trial of Interferon- Versus Conventional Chemotherapy in Chronic Myeloid Leukemia

Abstract

Several prospective randomized studies have shown that the treatment of chronic myeloid leukemia with interferon- (IFN-) prolongs the survival by comparison with conventional chemotherapy. However, although IFN- can induce cytogenetic responses, true complete remissions are rarely achieved and information on the long-term effects of IFN- treatment is limited. For that purpose, we updated and analyzed a prospective comparative trial of IFN- and conventional chemotherapy that was initiated in 1986. The first analysis of the trial was already published, and showed a survival advantage for IFN- (N Engl J Med 12:820, 1994). The observation period of living patients now ranges between 95 and 129 months and we examined the long-term effects of IFN- treatment, always by comparison with conventional chemotherapy and according to the intention-to-treat principle. The patients who were submitted to allogeneic bone marrow transplantation (BMT) in chronic phase (38 of 322 or 12%) were censored at the date of BMT. Seventy-three of the original 284 nontransplanted patients were alive, 56 (30%) in the IFN- arm and 17 (18%) in the chemotherapy arm. Forty-one patients overall (14%) were still receiving IFN-. In the IFN- arm 9 patients were in continuous complete cytogenetic remission and 11 were in major or minor cytogenetic remission. Median and 10-year survival of low-risk patients were 104 months (95% CI, 85 to 127 months) and 47% (95% CI, 36% to 59%) in IFN- arm versus 64 months (95% CI, 49 to 98 months) and 30% (95% CI, 16% to 44%) in chemotherapy arm (P = .03). Median and ten-year survival of non–low-risk patients were 69 months (95% CI, 56 to 76 months) and 16% (95% CI, 8% to 24%) in IFN- arm versus 46 months (95% CI, 39 to 61 months) and 5% (95% CI, 0% to 11%) in chemotherapy arm (P = .006). A low Sokal’s risk, hematologic response, and cytogenetic response were associated with a longer survival. No major or unusual side effects were recorded after the 5th year of IFN- treatment. Fourteen patients died in chronic phase, 9 (4%) in IFN- arm and 5 (5%) in chemotherapy arm, mainly of cardiovascular accidents (6 cases) and of other cancers (5 cases). We conclude that a policy of chronic treatment with IFN- maintained a significant survival advantage over conventional chemotherapy on a long-term basis and irrespective of the risk. However, the great majority of the long-term survivors were in the low-risk group. The question of treatment discontinuation was not addressed in this study. © 1998 by The American Society of Hematology.