title: 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?
abstract: 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.
authors.affiliation: Chronic Myelogenous Leukemia Group, Department of Hematology/Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. drkiim@medimail.co.kr
authors.forename: Dong Hwan ' Dennis '
authors.initials: DH
authors.lastname: Kim
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Sriharsha
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
mesh_terms: D001549:Benzamides; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use*; D012372:ROC Curve; D012074:Remission Induction; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate