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Comparing front-line therapies in older AML patients
Table 2. Univariate analyses, with dichotomization of Eastern Cooperative Oncology Group Performance Status (0-1 vs. ≥2).
Clinical Parameter
Sex
Male
Female Race/ethnicity
White
Other
Type of AML
De novo
Secondary
Prior hematologic disease
No
Yes
Karyotype
Favorable or intermediate
Adverse ECOG PS
0-1
2-4
Clinical trial as front-line therapy
No
Yes
Front-line therapy
HMA
HI therapy
LI therapy Supportive care
CCI
0-2
P
Reference
0.28
Reference 0.97
Reference
<0.0001
Reference <0.0001
Reference
<0.0001
Reference <0.0001
Reference
0.97
Reference 0.002 <0.0001 <0.0001
Reference
Hazard Ratio
1.08
1.00
1.56
1.52
1.82
2.10
1.00
1.32 1.92 3.38
1.28
1.16
1.01
1.12
0.72
0.88
95% Confidence Interval Lower Upper
0.94 1.24
0.78 1.27
1.36 1.78
1.33 1.74
1.57 2.11
1.77 2.48
0.83 1.20
1.11 1.57 1.50 2.46 2.80 4.07
1.06 1.55
1.09 1.25
0.98 1.05
1.07 1.17
0.68 0.78
0.84 0.91
≥3 0.011
Age at diagnosis (per 5-year increase)
BM blast at diagnosis (per 10% increase)
WBC, per 1 log increase
Platelets, per 1 log increase
Hemoglobin, per 1 log increase
<0.0001 0.42 <0.0001 <0.0001 <0.0001
AML: acute myeloid leukemia; BM: bone marrow; CCI: Charlson comorbidity Index; ECOG PS: Eastern Cooperative Oncology Group Performance Status; HI: high intensity; HMA:
hypomethylating agent; LI: low intensity; PB: peripheral blood; WBC: white blood cell.
High-intensity therapy resulted in superior median overall survival compared with supportive care (10.8 vs. 2.1 months; P<0.0001) and low-intensity therapy (10.4 vs. 5.9 months; P=0.001), and low-intensity therapy was superior to supportive care (5.9 vs. 2.1 months; P<0.0001).
Because 185 patients (36.5%) had prior hematologic dis- ease and thus received prior HMA, we created a univariate and multivariate model after excluding this subgroup, yielding a cohort of 795 HMA-naïve patients and assessed the impact of front-line treatment modality (Table 3). Variables that emerged as prognostically significant were identical to the variables from the multivariate model for the entire cohort. Within this HMA-naïve group, Kaplan- Meier analysis for overall survival was again noted to be superior in patients treated with HMA versus the other therapy groups, including the high-intensity (P=0.008),
low-intensity (P<0.0001), and supportive care treatment groups (P<0.0001) (data not shown).
A pairwise comparison using propensity score matching to minimize the selection bias for front-line treatment was used to create a multivariate model to validate the prognos- tic impact of the different variables. The multivariate model confirmed our previous findings regarding the effects of HMA versus high-intensity treatment (HR=0.78, 95%CI: 0.63-0.97; P=0.027) and HMA versus low-intensity treat- ment (HR=0.56, 95%CI: 0.42-0.74; P<0.0001) on mortality. In patients with non-adverse risk karyotype (intermediate- risk and favorable-risk), superiority of HMA treatment was also demonstrated compared to intensive chemotherapy (HR=0.71, 95%CI: 0.55-0.92; P=0.008). Low-intensity treat- ment was also inferior to high-intensity treatment (HR=1.32, 95%CI: 1.01-1.72; P=0.040) (data not shown).
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