Comprehensive evaluation of time‐to‐response parameter as a predictor of treatment failure following imatinib therapy in chronic phase chronic myeloid leukemia: Which parameter at which time‐point does matter?

Early recognition of high‐risk patient is important to improve long‐term outcomes following imatinib therapy for chronic myeloid leukemia (CML). Some controversy surrounds the question, which of short‐term response parameters at which time‐point, including complete cytogenetic response (CCyR) or major molecular response (MMR) at 6 or 12 months, is the best predictor for treatment outcomes. In this comprehensive analysis, we adopted landmark analysis method, time‐dependent Cox's proportional hazard model, and receiver‐operating characteristics (ROC) method to analyze time‐to‐response parameter as predictor of long‐term outcomes in 187 chronic phase (CP) CML patients. Regardless of the methods of analysis, earlier achievement of short‐term response such as CCyR or MMR could predict the higher probability of achieving better interim outcome (such as treatment failure or loss of response [LOR]). Similar to the findings from other studies, our ROC analysis provided cutoff time points for MMR (18–36 months) and CCyR (6–12 months) that were the best predictors for LOR or treatment failure, which can be an indirect evidence supporting the ELN recommendation. The patient who achieves short‐term response rapidly will have a lower risk of losing response or failing after imatinib therapy in CML patients. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.