Predictors of Long-Term Cytogenetic Response Following Dasatinib Therapy of Patients with Chronic-Phase Chronic Myeloid Leukemia (CML-CP).

Achievement of major and complete cytogenetic response on imatinib in newly diagnosed CML-CP has been associated with excellent survival. Dasatinib is a potent oral tyrosine kinase inhibitor with marked activity and good tolerability in patients with any-phase CML who have failed prior therapy, including imatinib.

To investigate factors predictive of cytogenetic response and survival outcomes for patients who receive dasatinib after imatinib failure.

Collated patient data from trials of dasatinib (START-C, START-R, and CA180-034) in patients with CML-CP were analyzed. All patients had failed prior treatment with imatinib as a result of resistance or intolerance. Patients with highly imatinib-insensitive BCR-ABL mutations (L248V, G250E, Q252H/R, Y253H/F, E255K/V, T315I/D, F317L, and H369P/R) were ineligible for START-R. Across the three trials, patients were administered dasatinib 50 (n=167) or 70 (n=655) mg twice daily, or 100 (n=165) or 140 (n=163) mg once daily. Analysis of efficacy parameters was performed on all patients receiving at least one dose of dasatinib (n=1150). A multivariate logistic regression model was applied to evaluate patient treatment characteristics as predictive factors for cytogenetic response.

After a median follow-up of 26 months, the rate of major cytogenetic response (MCyR) was 62% and of complete cytogenetic response (CCyR) was 51%. By multivariate analysis, the following were selected as independent favorable prognostic factors for achievement of MCyR: younger age, lower percentage of Ph+ cells, absence of the T315I mutation, prior MCyR with imatinib, imatinib intolerance (vs. resistance), no prior stem cell transplantation (SCT), shorter time from CML diagnosis to dasatinib therapy (Table 1). The same baseline factors independently predicted CCyR.

This study confirms the clinical efficacy of dasatinib among patients with CML-CP who have failed prior therapy. Furthermore, we identified baseline factors associated with improved response to dasatinib. Work to determine additional predictive factors for survival outcome with dasatinib is ongoing. The subgroups of patients who may not respond optimally to dasatinib are small, and a modification to their treatment regimen may be called for.

Jabbour:Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Bahceci:Bristol-Myers Squibb: Employment. Zhu:Bristol-Myers Squibb: Employment. Lambert:Bristol-Myers Squibb: Employment. Cortes:Bristol-Myers Squibb: Research Funding.