Cox proportional hazards model for EFS and OS in univariate and multivariate analyzes in patients entering first-line treatment
. | n . | EFS . | OS . | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | Univariate . | Multivariate n = 49 (387 events) . | Univariate . | Multivariate n = 469 (216 events) . | ||||||||||||||
. | HR . | 95% Cl . | P . | HR . | 95% Cl . | P . | HR . | 95% Cl . | P . | HR . | 95% Cl . | P . | ||||||
Age at FLT | ||||||||||||||||||
<60 y | 129 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
>60 y | 382 | 1.18 | 0.94 | 1.48 | .1465 | 2.20 | 1.58 | 3.06 | <.0001 | 1.32 | 0.9 | 1.94 | .1558 | |||||
Sex | ||||||||||||||||||
Female | 176 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
Male | 335 | 1.16 | 0.93 | 1.43 | .1855 | — | — | — | — | 0.95 | 0.73 | 1.25 | .7234 | — | — | — | — | |
RAI | ||||||||||||||||||
0+I+II | 208 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
III+IV | 299 | 1.52 | 1.24 | 1.86 | <.0001 | 1.28 | 1.04 | 1.56 | .0216 | 1.40 | 1.08 | 1.83 | .0120 | 1.13 | 0.85 | 1.51 | .3885 | |
B2M | ||||||||||||||||||
<3.5 mg/L | 234 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
>3.5 mg/L | 257 | 1.17 | 0.95 | 1.43 | .1330 | 2.05 | 1.56 | 2.69 | <.0001 | 1.62 | 1.2 | 2.19 | .0016 | |||||
TP53 mutation | ||||||||||||||||||
VAF continual, % | 141 | 1.02 | 1.01 | 1.02 | <.0001 | — | — | — | — | 1.02 | 1.01 | 1.02 | <.0001 | — | — | — | — | |
TP53 mutation | ||||||||||||||||||
No | 370 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
>10% VAF | 59 | 2.84 | 2.11 | 3.83 | <.0001 | 1.98 | 1.31 | 2.98 | .0013 | 3.75 | 2.67 | 5.26 | <.0001 | 2.81 | 1.65 | 4.78 | .0001 | |
1-10% VAF | 29 | 1.11 | 0.73 | 1.70 | .6269 | 1.16 | 0.75 | 1.77 | .5100 | 1.04 | 0.59 | 1.83 | .9020 | 1.68 | 1.08 | 2.62 | .0211 | |
<1% VAF | 53 | 1.34 | 0.97 | 1.84 | .0722 | 1.36 | 0.99 | 1.87 | .0620 | 1.69 | 1.12 | 2.56 | .0124 | 2.02 | 1.13 | 3.62 | .0174 | |
IGHV* | ||||||||||||||||||
Mutated | 142 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
Nonmutated | 362 | 1.92 | 1.50 | 2.46 | <.0001 | 1.76 | 1.35 | 2.28 | <.0001 | 2.07 | 1.47 | 2.92 | <.0001 | 2.78 | 1.9 | 4.06 | <.0001 | |
FISH† | ||||||||||||||||||
Normal | 105 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
Del(17p) | 41 | 3.24 | 2.18 | 4.81 | <.0001 | 2.01 | 1.19 | 3.39 | .0086 | 4.29 | 2.71 | 6.78 | <.0001 | 2.3 | 1.18 | 4.48 | .0140 | |
Del(11q) | 136 | 1.74 | 1.30 | 2.33 | <.0001 | 1.55 | 1.15 | 2.08 | .0041 | 1.41 | 0.96 | 2.09 | .0825 | 1.43 | 0.95 | 2.15 | .0888 | |
Trisomy 12 | 67 | 0.88 | 0.61 | 1.28 | .5162 | 0.87 | 0.6 | 1.26 | .4600 | 1.31 | 0.82 | 2.10 | .2648 | 1.1 | 0.66 | 1.84 | .7083 | |
Del(13q) | 160 | 0.95 | 0.71 | 1.28 | .7506 | 0.98 | 0.73 | 1.33 | .9000 | 1.12 | 0.76 | 1.66 | .5713 | 1.31 | 0.87 | 1.97 | .2009 | |
Inhibitor treatment‡ | ||||||||||||||||||
Yes | 119 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
No | 378 | — | — | — | — | — | — | — | — | 3.29 | 2.24 | 4.83 | <.0001 | 4.16 | 2.79 | 6.21 | <.0001 |
. | n . | EFS . | OS . | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | Univariate . | Multivariate n = 49 (387 events) . | Univariate . | Multivariate n = 469 (216 events) . | ||||||||||||||
. | HR . | 95% Cl . | P . | HR . | 95% Cl . | P . | HR . | 95% Cl . | P . | HR . | 95% Cl . | P . | ||||||
Age at FLT | ||||||||||||||||||
<60 y | 129 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
>60 y | 382 | 1.18 | 0.94 | 1.48 | .1465 | 2.20 | 1.58 | 3.06 | <.0001 | 1.32 | 0.9 | 1.94 | .1558 | |||||
Sex | ||||||||||||||||||
Female | 176 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
Male | 335 | 1.16 | 0.93 | 1.43 | .1855 | — | — | — | — | 0.95 | 0.73 | 1.25 | .7234 | — | — | — | — | |
RAI | ||||||||||||||||||
0+I+II | 208 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
III+IV | 299 | 1.52 | 1.24 | 1.86 | <.0001 | 1.28 | 1.04 | 1.56 | .0216 | 1.40 | 1.08 | 1.83 | .0120 | 1.13 | 0.85 | 1.51 | .3885 | |
B2M | ||||||||||||||||||
<3.5 mg/L | 234 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
>3.5 mg/L | 257 | 1.17 | 0.95 | 1.43 | .1330 | 2.05 | 1.56 | 2.69 | <.0001 | 1.62 | 1.2 | 2.19 | .0016 | |||||
TP53 mutation | ||||||||||||||||||
VAF continual, % | 141 | 1.02 | 1.01 | 1.02 | <.0001 | — | — | — | — | 1.02 | 1.01 | 1.02 | <.0001 | — | — | — | — | |
TP53 mutation | ||||||||||||||||||
No | 370 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
>10% VAF | 59 | 2.84 | 2.11 | 3.83 | <.0001 | 1.98 | 1.31 | 2.98 | .0013 | 3.75 | 2.67 | 5.26 | <.0001 | 2.81 | 1.65 | 4.78 | .0001 | |
1-10% VAF | 29 | 1.11 | 0.73 | 1.70 | .6269 | 1.16 | 0.75 | 1.77 | .5100 | 1.04 | 0.59 | 1.83 | .9020 | 1.68 | 1.08 | 2.62 | .0211 | |
<1% VAF | 53 | 1.34 | 0.97 | 1.84 | .0722 | 1.36 | 0.99 | 1.87 | .0620 | 1.69 | 1.12 | 2.56 | .0124 | 2.02 | 1.13 | 3.62 | .0174 | |
IGHV* | ||||||||||||||||||
Mutated | 142 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
Nonmutated | 362 | 1.92 | 1.50 | 2.46 | <.0001 | 1.76 | 1.35 | 2.28 | <.0001 | 2.07 | 1.47 | 2.92 | <.0001 | 2.78 | 1.9 | 4.06 | <.0001 | |
FISH† | ||||||||||||||||||
Normal | 105 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
Del(17p) | 41 | 3.24 | 2.18 | 4.81 | <.0001 | 2.01 | 1.19 | 3.39 | .0086 | 4.29 | 2.71 | 6.78 | <.0001 | 2.3 | 1.18 | 4.48 | .0140 | |
Del(11q) | 136 | 1.74 | 1.30 | 2.33 | <.0001 | 1.55 | 1.15 | 2.08 | .0041 | 1.41 | 0.96 | 2.09 | .0825 | 1.43 | 0.95 | 2.15 | .0888 | |
Trisomy 12 | 67 | 0.88 | 0.61 | 1.28 | .5162 | 0.87 | 0.6 | 1.26 | .4600 | 1.31 | 0.82 | 2.10 | .2648 | 1.1 | 0.66 | 1.84 | .7083 | |
Del(13q) | 160 | 0.95 | 0.71 | 1.28 | .7506 | 0.98 | 0.73 | 1.33 | .9000 | 1.12 | 0.76 | 1.66 | .5713 | 1.31 | 0.87 | 1.97 | .2009 | |
Inhibitor treatment‡ | ||||||||||||||||||
Yes | 119 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |
No | 378 | — | — | — | — | — | — | — | — | 3.29 | 2.24 | 4.83 | <.0001 | 4.16 | 2.79 | 6.21 | <.0001 |
Statistically significant parameters (P < .05) are shown in bold. Only parameters with P < 0.1 were analyzed in the multivariate models. The following patients with missing data were excluded: for EFS: RAI (n = 4), IGHV (n = 7), and FISH (n = 2); for OS: in addition to patients excluded in EFS, B2M (n = 16), allogeneic stem cell transplantation (excluded from category inhibitor treatment yes/no; n = 14). TP53 mutation VAF was analyzed as a continual parameter only in univariate analysis. In the multivariate model, presence of TP53 mutations was analyzed only as a categorical parameter.
CI, confidence interval; FLT, first-line treatment.
Based on 98% identity threshold.
According to Döhner et al.46
Treatment with BcR or bcl2 inhibitor later during the course of the disease.