ALBERT

Description: Abstract 3758 Background: The EUTOS score has been proposed by the European LeukemiaNet (ELN) as a new scoring system which is predictive for 18-month (mth) complete cytogenetic response (CCyR) and 5-year (yr) progression-free survival (PFS) in chronic phase (CP) chronic myeloid leukemia (CML) patients treated with first-line imatinib (IM) (Hasford et al, Blood 2011). The score is calculated using spleen size and basophil percentage and divides patients into low risk and high risk groups. However the EUTOS score was not validated in two studies, one which determined 8-yr overall survival (OS), PFS, CCyR and major molecular remission (MMR) (Marin et al, J Clin Oncol 2011); and in another which analysed 3-yr event-free survival, transformation-free survival and OS and overall CCyR and MMR (Kantarjian H et al, Blood 2012). Recent reports have suggested that Asian CML patients may have clinical and genetic differences compared to Causcasians, e.g. younger median age at presentation (Au et al, Int J Hem 2009) and genetic polymorphism leading to IM resistance (Pan et al, Nat Med 2012). Although a different disease, splenomegaly was also reported to be less frequent in Chinese patients with myelofibrosis (Xiao et al, Blood 2012). Given these differences, we sought to determine if the EUTOS score was predictive for clinical outcome and survival in Asian CP-CML patients treated with IM. Methods: A retrospective analysis was undertaken of CP-CML patients followed up in our institution from 2000–2012. All patients were treated with IM 400 mg within one year of diagnosis. The rates of 6-mth major cytogenetic response (MCyR), 12-mth CCyR, 18-mth CCyR, 12-mth MMR and 18-mth MMR were evaluated. MMR was defined as BCR-ABL transcript levels ≤ 0.1% by the International Scale. The probability of OS, PFS and failure-free survival (FFS) at 5 and 8 years was also determined. Progression was defined as transformation to accelerated or blast phase (AP/BP) or death from any reason. Failure was defined according to the 2009 ELN criteria or as an increase in dose of IM, change of therapy, transformation to AP/BP or death. Results: A total of 139 patients were included in the analysis. The median age at presentation of CML was 45 yrs (range 16–88) with 64% Chinese, 17% Malays and 8% Indians. There was 69% in the low risk EUTOS group. Cytogenetic responses were significantly better in the low risk group compared to the high risk group with 6-mth MCyR rates of 82% vs 48% (p

Description: Introduction: Long-term survival rates among patients with chronic-phase chronic myeloid leukaemia (CP-CML) have remarkably improved since the introduction of imatinib, a BCR-ABL1 tyrosine-kinase inhibitor (TKI), as the standard first-line therapy. Several prognostic scores have been employed to predict clinical response and survival of CP-CML patients treated with TKIs. The EUTOS long-term survival (ELTS) score was recently introduced and shown to predict the probability of CML-specific death in long-term surviving patients on imatinib therapy, more effectively than the existing scores. The ELTS score was calculated by a formula that included age at diagnosis, spleen size below costal margin, platelet count and blast percentage in peripheral blood as prognostic factors. In our study, we evaluated the ELTS score in predicting the probabilities of CML-specific death, long-term overall survival (OS) and progression-free survival (PFS) rates in Asian CML patients treated with imatinib. As genetic differences, particularly the BCL-2 like 11 (BIM) deletion polymorphism, have been shown to confer intrinsic resistance to imatinib in East-Asian patients, we also explored the role of BIM deletion polymorphism profiling as a prognostic biomarker for CML-specific death among different risk groups stratified by the ELTS score. Methods: A retrospective analysis was performed on CP-CML patients treated with first-line imatinib within one year of diagnosis in Singapore General Hospital from June 2001 to November 2014. The ELTS score was obtained with online calculator at www.leukemia-net.org. Low-risk group was defined as a score ≤1.568, intermediate-risk group as a score 〉1.568 but ≤2.2185, and high-risk group as a score 〉2.2185. Progression was defined as transformation to accelerated or blast phase or death from any cause. OS and PFS were calculated with the Kaplan-Meier method and compared by the log-rank test. Cumulative incidence probabilities of CML-specific death were compared by the Gray test. Findings: 134 patients were included for analysis. 63% were Chinese, 17% were Malays, 8% were Indians and 12% were of mixed ethnic origin. Median age at diagnosis was 45 years and 60% were male. Median follow-up was 7.7 years (range: 0.4 to 13.2 years). 17 deaths out of 134 patients (13%) were recorded, of which 11 were CML-specific (65%). 54% of patients were categorised as low-risk, 36% as intermediate-risk and 10% as high-risk by the ELTS score. The cumulative incidence probabilities of CML-specific death at 10 years were 43% in high-risk (hazard ratio (HR): 11.76, 95% confidence interval (CI): (2.32, 59.71), p=0.003) and 9% in intermediate-risk (HR: 2.24, 95% CI: (0.37, 13.49), p=0.38) compared to 3% in low-risk groups.10-year OS probabilities were 50%, 82% and 93% in high-, intermediate- and low-risk ELTS groups respectively (p=0.001). 10-year PFS probabilities were 50%, 84% and 89% in high-, intermediate- and low-risk ELTS groups respectively (p=0.004). Among 103 East-Asian patients with low- and intermediate-risk ELTS sub-groups, 15% harboured BIM deletion polymorphism. The probability of CML-specific death at 10 years in this subset was 16% with BIM deletion polymorphism, but 4% without polymorphism (HR 4.30, 95% CI: (0.76, 24.35), p=0.099). 10-year OS probabilities in the subset were 75% and 89% in patients with and without BIM deletion polymorphism respectively (p=0.014). Conclusions: The ELTS score was able to predict the probability of CML-specific death and identify high-risk patients in our multi-racial Asian CML patients treated with imatinib. Genetic profiling using BIM deletion polymorphism provided further stratification by identifying a subset of inferior long-term survivors with high probability of CML-specific death among otherwise non high-risk patients. Disclosures Chuah: Bristol-Myers Squibb: Honoraria; Novartis: Honoraria; Chiltern: Honoraria.