Page 74 - Haematologica August 2018

G.J. Roboz et al.
Figure 1. Treatment schema.
Statistical analysis
The primary study end point was to determine the safety and toxicity of this novel treatment regimen combining decitabine and plerixafor. The secondary clinical end points included overall response rate and overall survival. Overall survival was measured in months from cohort assignment to date of death or last follow- up date. The overall response rate (ORR) calculation included CR, CRi and PR. Descriptive statistics (i.e. median, range, frequency, and percent) were calculated to characterize the study population. Overall survival (OS) was assessed by Kaplan-Meier survival analysis, and univariate associations between demographic/clini- cal variables of interest and OS were assessed by the log-rank test. The independent effect of demographic/clinical predictors of inter- est on OS was assessed by multivariable Cox proportional haz- ards regression analysis. Adjusted hazard ratios (HR) were com- puted and 95% confidence intervals (95%CI) for hazard ratios and median OS time estimates are presented to assess the precision of the obtained estimates. Median follow-up time for the study group was computed based on survivors. Associations between demographic/clinical variables of interest and overall response were evaluated by the χ2 test or Fisher’s exact test, as appropriate. All P-values are two-sided with statistical significance evaluated at the 0.05 alpha level. All analyses were performed in SPSS v.24.0 (SPSS Inc., Chicago, IL, USA) and Stata v.14.0 (StataCorp, College Station, TX, USA).
Correlative scientific studies
Details of correlative scientific studies and mutational profiling can be found in Online Supplementary Appendix 1.
Results
Patients' characteristics
Ninety-five newly diagnosed AML patients were screened for eligibility and 69 patients were enrolled onto the study between June 2011 and January 2013. Of the 26 patients ineligible for study participation, 18 were reclas- sified as having myelodysplastic syndrome and 8 patients chose to receive standard induction chemotherapy. Baseline characteristics are presented in Table 1. The base- line mutational profile of the cohort is presented in Figure 2. The most frequently observed mutations were in RUNX1 (38%), TET2 (31%), ASXL1 (30%), SRSF2 (30%), DNMT3A (28%), BCOR (18%), and TP53 (18%). The median age at diagnosis was 73 years (range 56-87 years);
Table 1. Patients' baseline characteristics.
Characteristic or demographic
Age at diagnosis, years Median
Range
Sex Female
Male
ECOG performance status 0
1 2
N. of patients %
73 56-87
31 44.9
38 55.1
12 17.4 44 63.8 13 18.8
39 56.5
30 43.5
30 43.5 39 56.5
31 44.9
38 55.1
14 20.3 55 79.7
CALGB cytogenetic risk classification20 Intermediate
Adverse
Antecedent hematologic disorder Present
Not present
Treament-related AML Yes
No
Prior hypomethylating agent Yes
No
Bone marrow blasts
Median 54 Range 6-99
Ejection fraction
Median 62
1310
Range
Creatinine clearance ≤50 mL/min Bilirubin >1.5 x ULN
White blood cell count >30x109/L
30-76
28 40.6
3 4.4 10 14.5
N: number; ECOG: Easter Cooperative Oncology Group; CALGB: Cancer and Leukemia Group B; AML: acute myeloid leukemia; ULN: upper limit of normal. Based on Byrd et al. CALGB cytogenetic risk criteria.20
55% were male. Approximately 80% of the patients had Eastern Cooperative Oncology Group (ECOG) perform- ance status (PS) 0-1 and the remainder had ECOG PS 2. Forty-four percent of patients had adverse cytogenetics, 44% had an antecedent hematologic disorder, and 45% had therapy-related AML. The median bone marrow
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