Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase

BACKGROUND: The European LeukemiaNet recommendations for chronic myeloid leukemia (CML) defined a group of patients with suboptimal response to imatinib. The significance of this response was not well defined. METHODS: The significance of having had a suboptimal response during imatinib therapy among 281 patients with CML treated with standard-dose (n = 73) or high-dose (n = 208) imatinib was investigated. RESULTS: Rates of suboptimal response at 6, 12, and 18 months were 4%, 8%, and 40%, respectively, and were not influenced by Sokal risk score. Patients with a suboptimal response at 6 months had a significantly lower probability of eventually achieving a complete cytogenetic response (CCyR) compared with those with an optimal response (30% vs 97%; P < .001), and their event-free survival (EFS) and transformation-free survival (TFS) were found to be similar to those with criteria for failure at this time point. Suboptimal response at 12 months defined a group with a similar TFS as those with optimal response, but with worse EFS. In contrast, patients with a suboptimal response at 18 months had outcomes that were similar to those patients with an optimal response. A multivariate analysis confirmed the significance of response category after adjusting for pretreatment characteristics and imatinib dose. CONCLUSIONS: The results of the current study suggested that suboptimal response was a heterogeneous category, and some patients had an outcome that mirrored that of patients with failed therapy. Interventions aimed at improving this outcome are required.