Abstract

Introduction

One of the most significant novelty of the revised version of the European LeukemiaNet (ELN) recommendations for the management of chronic myeloid leukemia (CML) patients is that an earlier achievement of complete cytogenetic response (CCyR), at 6 months, and major molecular response (MMR), at 12 months, is regarded as optimal. Moreover, the prognostic value of the depth of molecular response at three months (i.e. BCR-ABL/ABL ratio ≤10%) is recognized. We have previously reported that EUTOS score is able to predict long term outcome of imatinib therapy, and that high-risk patients had a non-statistically significant lower probability to achieve all the cytogenetic and molecular endpoints defined as optimal by 2009 ELN recommendations.

Aims and Methods

We retrospectively evaluated our cohort of CML patients treated with front-line standard dose imatinib to test the ability of EUTOS and Sokal scores to foresee 2013 ELN-defined optimal response to therapy. A total of 314 consecutive patients treated with imatinib 400 mg daily for early chronic phase CML were analysed. Median age at diagnosis was 57 years (range: 19-85 years). According to the Sokal score there were 133 (42%) low risk, 127 (40%) intermediate risk, 52 (17%) high risk and 2 (1%) unknown risk cases, respectively. The distribution according to the EUTOS score was: 289 patients (92%) in the low-risk and 25 (8%) in the high-risk group. Partial cytogenetic response (PCyR) and CCyR were defined as 1-35% and 0% Ph+ metaphases, respectively; major molecular response (MMR) was defined as BCR-ABL <0.1%IS. For the purposes of this analysis, and as suggested by the ELN experts, we divided patients into low and high risk also according to Sokal score, thus considering low and intermediate risk as one group.

Results

Considering EUTOS score, at the 3 months timepoint we observed a significant higher rate of optimal molecular response (≤10%) in low risk (76%) compared to high risk (52%, p=0.03) patients, while there was a only trend for cytogenetic response (Ph+ ≤35%) (86% vs 75%, p=0.20). At 6 months, both cytogenetic (CCyR) and molecular (≤1%) optimal responses were higher in the low risk group: 76% vs 46% (p=0.003) and 67% vs 33% (p=0.004), respectively. At 12 months, 58% of low risk patients were in MMR, compared to 41% in the high risk group (p=0.20). Dividing patients according to Sokal score in two groups of intermediate-low (n=260) and high (n=52) risk, we found a significant difference in the rates of cytogenetic response both at 3 (88% vs 72%, p=0.03) and at 6 (79% vs 48%, p=0.0001) months, while no significant differences were seen in molecular response at 3 (76% vs 62% p=0.13), 6 (67% vs 50%, p=0.08) or 12 (56% vs 55%, p=1.00) months.

Conclusions

Our results suggest that EUTOS score is able to predict optimal response to imatinib, in particular achievement of molecular response at 3 months, a marker of emerging importance in foreseeing long-term outcome, and of CCyR at 6 months, that has been associated with superior progression-free and overall survival. Sokal score predict sensibly cytogenetic responses, but seems less efficacious in identifying patients that will achieve optimal molecular endpoints.

Table 1
 Eutos Low (n=289) Eutos High (n=25) Sokal Low+Int (n=260) Sokal High (n=52) 
3-mo. CyR 
Ph+ ≤35% 175 15 0.20 160 29 0.03 
Ph+ >35% 29 23 11 
n.e. / n.d. 85  77 12  
3-mo. MR 
≤10% IS 118 11 0.03 108 21 0.13 
>10% IS 37 10 34 13 
n.e. / n.d. 134  118 18  
6-mo. CyR 
Ph+ 0% 179 11 0.003 169 21 0.0001 
Ph+ ≥1% 57 13 44 23 
n.e. / n.d. 53  47  
6-mo. MR 
<1% IS 118 0.004 106 18 0.08 
≥1% IS 59 14 53 18 
n.e. / n.d. 112  101 16  
12-mo. MR 
≤0.1% IS 108 0.20 96 18 1.00 
>0.1% IS 77 10 75 15 
n.e. / n.d. 104  89 19  
 Eutos Low (n=289) Eutos High (n=25) Sokal Low+Int (n=260) Sokal High (n=52) 
3-mo. CyR 
Ph+ ≤35% 175 15 0.20 160 29 0.03 
Ph+ >35% 29 23 11 
n.e. / n.d. 85  77 12  
3-mo. MR 
≤10% IS 118 11 0.03 108 21 0.13 
>10% IS 37 10 34 13 
n.e. / n.d. 134  118 18  
6-mo. CyR 
Ph+ 0% 179 11 0.003 169 21 0.0001 
Ph+ ≥1% 57 13 44 23 
n.e. / n.d. 53  47  
6-mo. MR 
<1% IS 118 0.004 106 18 0.08 
≥1% IS 59 14 53 18 
n.e. / n.d. 112  101 16  
12-mo. MR 
≤0.1% IS 108 0.20 96 18 1.00 
>0.1% IS 77 10 75 15 
n.e. / n.d. 104  89 19  
Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.