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TUMOR MUTATIONAL BURDEN (TMB) AND
IMMUNE GENE EXPRESSION SIGNATURES
(PAIRED DNA/RNA DATA SET, n = 301)
•
High tumor mutational burden (using the top third as a threshold) added positive prognostic value to immune gene signatures
in the placebo arm (high IFN-γ and high TMB associated with longer RFS)
•
In the dabrafenib + trametinib arm, IFN-γ gene signature identified patients with longer RFS independently of TMB status
TMB high/
IFN-
γ
high:
> 60% RFS
TMB low/
IFN-
γ
low:
≈ 20% RFS
PRESENTED BY GV LONG AT ESMO 2018
Placebo
RFS, %
0
0
20
40
60
80
100
10 20 30
40
50 60
28
21
16 16
13
3
1
48
28
20 17
14
55
22
16 13
9
4
6
23
15
12 12
10
4
Dabrafenib + Trametinib
RFS, %
0
0
20
40
60
80
100
10 20 30 40 50 60
27
27
21
19
14
6
47
42
37
35
25
54
43
32
21
13
1
7
19
18
11
8
8
3
TMB high, IFN-
γ
high
TMB high, IFN-
γ
low
TMB low, IFN-
γ
high
TMB low, IFN-
γ
low
Months
TMB low, IFN-
γ
high
TMB high, IFN-
γ
high
TMB high, IFN-
γ
low
TMB low, IFN-
γ
low
TMB high, IFN-
γ
high
TMB high, IFN-
γ
low
TMB low, IFN-
γ
high
TMB low, IFN-
γ
low
TMB low, IFN-
γ
high
TMB high, IFN-
γ
high
TMB high, IFN-
γ
low
TMB low, IFN-
γ
low
Months
0
0
0
0
0
0
0
No. at risk
No. at risk