AN EXPLORATORY ANALYSIS FROM 3-YEAR DASISION FOLLOW-UP EXAMINING THE IMPACT ON PATIENT OUTCOMES OF EARLY COMPLETE CYTOGENETIC RESPONSE AT 3 MONTHS AND MAJOR MOLECULAR RESPONSE AT 12 MONTHS

Sborník

Background. In the phase 3 DASISION trial of dasatinib v imatinib in patients with newly diagnosed chronic myeloid leukemia-chronic phase (CML-CP), dasatinib showed superior efficacy over imatinib with higher rates of complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months, lower rates of transformation and acceptable tolerability (Kantarjian et al. Blood 2012;119:1123). The value of earlier and deeper response in outcome prediction has emerged in CML-CP patients receiving first-line imatinib. A recent analysis of patients treated with dasatinib or nilotinib as initial therapy for CML has shown that patients who achieve a CCyR at 3 months have significantly higher probability of event-free survival at 3 years than those without CCyR (Jabbour et al. JCO 2011;29:4260). Aims. Explore landmark analyses of CCyR at 3 months and MMR at 12 months on PFS. Methods. Patients with CML-CP diagnosed within 3 months were randomized to receive dasatinib 100 mg QD (n=259) or 400 mg imatinib QD (n=260). MMR was defined as a BCR-ABL/ABL transcript level of ≤ 0.1% on the international scale (3-log reduction compared to the standardized baseline). PFS events considered were increasing WBC; loss of complete hematologic response or major cytogenetic response; progression to AP/BP; or death from all causes. Kaplan Meier curves of progression in patients achieving or not achieving CCyR at 3 months were generated. Results. Patients receiving dasatinib v imatinib had faster responses; median time to CCyR and MMR was 3.2 v 6.0 months and 15 v 36 months, respectively. Higher rates of CCyR at 3 months were achieved in patients receiving dasatinib v imatinib (54% v 31%). The rates of MMR at 12 months were also higher for patients receiving dasatinib v imatinib (47% v 28%). Of those patients who achieved MMR at 12 months, 97% and 92% of patients receiving dasatinib v imatinib, respectively, maintained their MMR at 24 months. In a landmark analysis, CCyR at 3 months was associated with higher PFS rates (p-value 0.0372). Similarly, achieving an MMR at 12 months was also associated with higher PFS (p-value 0.0380). Given the low number of events and exploratory nature of this analysis these data should be interpreted cautiously. Additional analyses will be reported exploring measures potentially predictive of improved outcome. Updated analyses will be presented with minimum 36-month follow-up. Conclusions. In patients with newly diagnosed CML-CP, first-line dasatinib resulted in faster and deeper responses compared with imatinib. The achievement of an early deep response at 3 and 12 months appear predictive of improved PFS in patients with early CML-CP treated with tyrosine kinase inhibitors.

Haematologica, 2012; 97(s1):  454