Page 111 - 2021_09-Haematologica-web

Mutations in ET treated with imetelstat
Table 1. Characteristics of patients.
Pt. Age at Sex Years Prior HR
dg since therapies, dg n.
1 52 F 20.7 3 CR
2 43 M 4.6 2 CR
3 60 M 3.3 3 CR
4 67 F 19.9 3 CR
5 55 F 0.3 1 CR
6 69 M 7.7 2 CR
7 83 F 1.8 2 CR
8 64 M 5.7 1 CR
9 48 M 1.3 1 CR
10 78 F 1.9 3 CR
11 56 F 12.1 2 CR
12 80 M 11.8 2 CR
13 46 F 6.9 3 CR
14 77 M 1 2 CR
15 47 M 11.6 4 PR
16 21 F 13.4 2 CR
17 61 F 10.9 3 CR
18 59 F 24.9 3 PR
Duration of imetelstat therapy, months
18.5 28.9 23.5 18.3
25.2 18.7 13.2 14.5 10.8
15.9
12.1 33.2
36.7 23.3
Duration of response, months
18.3+ 29.8+ 24+ 17.6
23.9+ 17.5+ 2.4 16.5+ 9.7+
Driver mutation
JAK2V617F CALR Type 1 JAK2 V617F CALR Type 2
JAK2 V617F JAK2 V617F none CALRType1 JAK2 V617F
Reduction Best in allele MR
burden at BR, %
-96 MMR -31 PMR -82 MMR -38 PMR
-94 MMR -24 No na na -48 PMR -100 MMR
Additional mutations at study entry
TP53p.Arg249Lys TET2 p.Tyr1608Leufs*6
DNMT3A p.Tyr735Cys EZH2 p.Asp293Ala SF3B1 p.Lys666Arg TET2 p.Arg1465Ter TP53 p.His179Leu
SF3B1 p.Lys700Glu
ASXL1
p.Gly646Trpfs*12 U2AF1 p.Gln157Pro CBL c.1432-1G>A DNMT3Ap.M880V TET2 p.Met1772Cysfs*48
DNMT3A p.Ala644Thr
DNMT3A p.Arg688His DNMT3A c.2597+1G>A
ASXL1 p.Tyr591Ter DNMT3A p.Gly722Asp
Late-emerging mutations*
TP53 p.Cys135Trp
14.5+
10.9 none na na
JAK2V617F
-90 MMR
31.3+ CALR del1092-1124
29.5 MPL 21.7+ JAK2 V617F
-55 MMR
-66 MMR -72 MMR
-15 No -96 MMR -82 MMR 0 No
IDH1 p.Arg132His
TET2 p.Ser137Gly
7.8 3.8+ CALRType1
24 22.4+
16.6 10.7
6.9 4.2
JAK2 V617F
JAK2 V617F
MPL
Dg: diagnosis; HR: hematologic response; BR: best molecular response; MR: molecular response; MMR: major molecular response (>50% mutant allele burden reduction from baseline); PMR: partial molecular response (25% to 49% mutant allele burden reduction from baseline); No, no response; +, continued on treatment; * after best molecular response of the driver mutation.
Figure 1. Frequency and distribution of mutations by patient at study entry.
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