Abstract 3769

Background:

Until recently, prognosis of pts with CML treated with TKI was based on scores developed in the chemotherapy and interferon era. Hasford and colleagues [Blood. 2011;(118):686–692] have identified the EUTOS score, using the percentage of basophils and spleen size, as a significant tool to predict the probability of achieving 18-month complete cytogenetic response (CCyR) and progression-free survival in patients treated with imatinib.

Aims:

To validate the EUTOS score in an independent MDACC cohort of pts, with early CML-CP treated with standard-dose imatinib, high-dose imatinib, dasatinib, and nilotinib, and its ability to predict transformation-free survival (TFS), event-free survival (EFS) and overall survival (OS).

Methods:

465 consecutive pts with newly diagnosed CML–CP (0 – 6 months from diagnosis to TKI treatment) were treated with imatinib 400 mg daily (n=71), imatinib 800 mg daily (n=208), and 2nd TKIs (n=186; dasatinib n=88, nilotinib n=98) in sequential phase II trials. Entry criteria were similar for all trials. EUTOS score = (7 x basophils %) + (4 x spleen cm BCM). A EUTOS score of >87 indicates high-risk and ≤87 low-risk.

Results:

465 pts with CML-CP were assessed. Median age was 47 years (range, 15–85). Median time from diagnosis to TKI therapy was 1 month (range, 0 to 6). 319 (69%), 112 (24%), and 34 (7%) pts were in low, intermediate, and high-Sokal score category, respectively. Median basophils percentage at baseline was 3 (range, 0 to 19). Median splenomegaly size was 0 cm (range, 0 to 30). 118 pts (25%) received previous cytoreduction therapy. Median follow-up was 117 months (range, 16 to 130) for pts receiving standard-dose imatinib, 88 months (range, 4 to 118) for those receiving high-dose imatinib, and 30 months (range, 3 to 69) for those receiving 2nd TKI. The overall CCyR rates were 87%, 91%, and 95%, respectively. The 4-year EFS, TFS, and OS rates for the whole group were 84%, 94%, and 95%, respectively. Overall, of the 465 pts, 427 (92%) were in low EUTOS score category (Table 1). Pts with low EUTOS score had higher rates of CCyR at anytime compared to pts with high EUTOS score (93% versus 81%, p=0.02). This difference was mainly significant among pts receiving 2nd TKI (p=0.03) while it was not different among pts receiving imatinib (p=0.27). There was no difference in the rates of major molecular response (85% versus 81%, p=0.48) between pts with low and high EUTOS score. There was no difference in TFS, EFS, and OS rates between pts with low and high EUTOS score, overall and among specific therapy (Table 1).

Conclusion:

Eight percent of pts with CML-CP treated at MDACC are of high EUTOS score. In this population, the EUTOS score was not predictive for overall MMR, TFS, EFS, and OS.

ParameterOverallLow EUTOS scoreHigh EUTOS scorep-value
N=465427 (92%)38 (8%)
CCyR (%) Overall (evaluable=454) 92 93 81 0.02 
    Imatinib 90 91 82 0.27 
    400 mg 87 86 100 1.0 
    800 mg 91 92 79 0.08 
 2nd TKI 95 96 80 0.03 
MMR (%) Overall (evaluable=452) 85 85 81 0.48 
    Imatinib 84 85 82 0.76 
    400 mg 78 77 100 1.0 
    800 mg 86 87 79 0.30 
 2nd TKI 86 86 80 0.46 
4-year EFS (%) Overall 84 84 81 0.71 
    Imatinib 81 82 72 0.20 
    400 mg 78 80 50 0.34 
    800 mg 82 83 76 0.29 
 2nd TKI 89 88 100 0.16 
4-year TFS (%) Overall 94 94 97 0.51 
    Imatinib 93 93 94 0.33 
    400 mg 89 90 67 0.47 
    800 mg 94 93 100 0.46 
 2nd TKI 97 97 100 0.53 
4-year OS (%) Overall 95 95 100 0.88 
    Imatinib 94 94 100 0.75 
    400 mg 93 92 100 0.34 
    800 mg 95 94 100 0.32 
 2nd TKI 99 99 100 0.64 
ParameterOverallLow EUTOS scoreHigh EUTOS scorep-value
N=465427 (92%)38 (8%)
CCyR (%) Overall (evaluable=454) 92 93 81 0.02 
    Imatinib 90 91 82 0.27 
    400 mg 87 86 100 1.0 
    800 mg 91 92 79 0.08 
 2nd TKI 95 96 80 0.03 
MMR (%) Overall (evaluable=452) 85 85 81 0.48 
    Imatinib 84 85 82 0.76 
    400 mg 78 77 100 1.0 
    800 mg 86 87 79 0.30 
 2nd TKI 86 86 80 0.46 
4-year EFS (%) Overall 84 84 81 0.71 
    Imatinib 81 82 72 0.20 
    400 mg 78 80 50 0.34 
    800 mg 82 83 76 0.29 
 2nd TKI 89 88 100 0.16 
4-year TFS (%) Overall 94 94 97 0.51 
    Imatinib 93 93 94 0.33 
    400 mg 89 90 67 0.47 
    800 mg 94 93 100 0.46 
 2nd TKI 97 97 100 0.53 
4-year OS (%) Overall 95 95 100 0.88 
    Imatinib 94 94 100 0.75 
    400 mg 93 92 100 0.34 
    800 mg 95 94 100 0.32 
 2nd TKI 99 99 100 0.64 
Disclosures:

Cortes:BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.