Page 112 - 2019_05-HaematologicaMondo-web

C. Michel et al.
Table 1. Univariate Cox regression estimating the influence on relapse-free survival after reduction to imatinib at 400 mg.
Variable
Variables recorded at diagnosis
Age (years)
Gender
Male
Female
Spleen size below costal margin (cm) White blood cell count (x109/L) / 100 Blasts in peripheral blood (%) Eosinophils in peripheral blood (%) Basophils in peripheral blood (%) Platelet count (x109/L) /1000
Sokal score
Low risk
Intermediate risk
High risk
Euro score
Low risk
Intermediate risk
High risk
EUTOS score
Lowrisk
High risk
ELTS score
Lowrisk
Intermediate risk
High risk
Variables recorded under treatment and their influence after stopping treatment at 800mg/day
Upper P
95%CI ratio limit for hazard ratio
n/Loss Estimationof
Standard deviation of estimated β
Hazard ratio
Lower
95%CI limit for hazard ratio
of MMR
coefficient β
-1.04 0.16 1.01 0.24 0.19 0.09 -2.44
1.08 0.06 0.25 0.11 0.07 0.07 2.35
0.36 1.17 2.76 1.27 1.21 1.10 1.00
0.02 1.03 1.69 0.99 1.02 0.93 0.00
- - 2.08 - 1.31 0.02 4.73 0.0001 1.55 0.06 1.37 0.03 1.25 0.24 3.40 0.24
0.03
1.00
0.94
68/7
68/7
48/6
20/1
68/7
68/7
68/7
68/7
68/7
68/7
68/7
29/2
27/3
12/2
68/7
30/1
34/4
4/2
68/7
62/4 baseline - - - - -
-0.001
baseline - - -
1.06 0.97 0.28
baseline - - -
0.57
0.60
0.91
1.82
0.30
- - 13.79 - 24.15 -
1.42 3.04
1.12 1.23
4.13 20.98
0.61 1.99
- - 80.86 - 454.17 -
1.01
2.87
0.34
1.05
baseline - - -
0.04
0.01
6/3 2.26 0.77 9.56 1.88 43.50 -
68/7
44/1 baseline - - - - - 19 / 4 2.30 1.12 9.98 1.48 195.25 -
5/2 3.17 1.23 23.71 2.25 513.27 -
Time with 800mg dosage, months
Time from start of 800mg until MMR, months
Time from MMR until end of 800mg, months
CI: Confidence Interval; MMR: major molecular remission; EUTOS: European Treatment and Outcome Study; ELTS: EUTOS long-term survival.
68 / 7 68 / 7 68 / 7
-0.05 0.03 0.13 0.05 -0.15 0.07
0.95 0.891 0.998 0.04 1.14 1.02 1.27 0.02 0.86 0.72 0.96 0.0006
0.01
Patients' characteristics are shown in Online Supplementary Table S1. Median age was 52 years and 71% of the 68 patients were male.
Treatment course of patients with imatinib dose reduction to 400 mg
Twenty-five of the 68 patients on high-dose imatinib (37%) started their primary treatment directly with 800 mg/day (first treatment interval). Forty patients (59%) increased to 800 mg/day after a first period of 400 mg ima- tinib. Three patients only started the 800 mg imatinib dose later.
Median time on high-dose imatinib therapy was 31 months (range: 6-98 months) for the 68 patients who later reduced imatinib treatment to 400 mg (Online Supplementary Table S1). In this cohort, the median dura-
tion of treatment with 400 mg/day after dose reduction was 34 months (range: 6-78 months). For 53 out of 68 patients (78%), this was the last reported treatment and dose. Five patients (7%) eventually stopped any TKI ther- apy following imatinib dose reduction to 400 mg. In one patient, no information regarding treatment after dose reduction to 400 mg was available. The remaining 9 out of 68 patients (13%) received a more potent ABL-kinase inhi- bition: 600 mg imatinib (n=1), 800 mg imatinib (n=5), nilo- tinib (n=2), or dasatinib (n=1).
Molecular relapse-free survival after imatinib dose reduction to 400 mg
Seven of 68 patients experienced a loss of MMR during the reduction interval (Figure 2). This resulted in a 1-year molecular relapse-free survival (RFS) of 90% (95%CI: 81-
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haematologica | 2019; 104(5)