The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up

Abstract

Background: Imatinib mesylate is the first line treatment for chronic myeloid leukemia. The advent of imatinib increased survival significantly in patients in an advanced phase of the disease. However, few long-term data on the outcome of these patients based on large, prospective and controlled trials are available.

Design and methods: A phase 2 multicenter trial of the use of imatinib 600 mg/daily in patients with accelerated phase chronic myeloid leukemia was sponsored and promoted by the Italian Cooperative Study Group on Chronic Myeloid Leukemia in 2001.

Results: One hundred and eleven patients were enrolled; the median follow-up of the 41 living patients is 82 months (range, 73-87). One hundred and seven patients (96%) returned to chronic phase and 79 patients (71%) achieved a complete hematologic response. Cumulative best rates of major cytogenetic response and complete cytogenetic response were 30% and 21%, respectively. All responses were maintained for a minimum of 4 weeks. At last follow-up, four patients were alive in complete remission after allogeneic transplant, 16 patients (14%) had switched to a second generation tyrosine kinase inhibitor and 21 patients (19%) were alive on imatinib therapy. No late toxicities were observed. Progression-free survival and event-free survival rates were 36.5% and 15%, respectively, at 7 years. The median survival time was 37 months, and was significantly associated with the achievement of a complete hematologic response or a complete cytogenetic response.

Conclusions: Imatinib may induce durable responses, associated with prolonged survival, in patients with accelerated phase chronic myeloid leukemia.

Figures

Figure 1.

(A) Duration of complete hematologic response (CHR) and of (B) complete cytogenetic response (CCgR) by landmark analysis at 3 months. Fifty-six percent and 81% of the patients who had achieved a CHR or a CCgR, respectively, maintained the response during follow-up.

Figure 2.

(A) Overall survival, (B) progression-free survival and (C) event-free survival. At 7 years, the overall survival rate of the entire study population was 43% (95% CI 33%–53%), the progression-free survival rate was 36.5% (95%CI, 27%–45%), and the event-free survival rate was 15% (95% CI, 7%–26.5%).