Page 308 - Haematologica March 2020

C. Zaninetti et al.
nia (ANKRD26-RT);19 three with thrombocytopenia caused by WAS mutations (2 with X-linked thrombocy- topenia, XLT, and 1 with Wiskott-Aldrich syndrome, WAS);20,21 two with monoallelic Bernard-Soulier syndrome (mBSS) caused by the Ala156Val mutation of GPIbα;22 and one with thrombocytopenia deriving from an ITGB3 mutation (ITGB3-RT).23 The patients’ mean platelet count was 40.4x109/L. Table 1 and Online Supplementary Table S4 describe the features of the study population at baseline.
Part 1 of the study
Twenty-three patients completed part 1 of the study, whereas one patient with ANKRD26-RT discontinued treatment early because of an adverse event (see below). Primary endpoint
Table 1. Main features of the study population at baseline. Overall MYH9-RD
Responses in part 1 of the study are summarized in Table 2 and detailed in Online Supplementary Tables S5 and S6. Twenty-one of the 23 evaluable patients [91.3%, 95% confidence interval (95% CI): 72.0-98.9] obtained a response according to the study criteria: 11 patients (47.8%) achieved a major response and ten (43.5%) a minor response. Two patients (8.7%) did not respond (one with ANKRD26-RT and the patient with ITGB3-RT). Most patients with MYH9-RD and the two subjects with mBSS obtained a major response, whereas most patients with ANKRD26-RT and the three subjects with XLT/WAS achieved a minor response (Table 2).
The mean platelet count at the end of part 1 of the study was 104.9x109/L (P<0.001 compared to baseline). The mean increase in platelet count with respect to baseline
ANKRD26-RT XLT/WAS mBSS ITGB3-RT Patients,n. 24 9 9 3 2 1
M/F, n. of patients
Age, years - mean [SD]
Platelet count,1 x109/L - mean [SD]
14/10 41.1 [13.7] 40.1 [22.4] 13
2/7 42.9 [14.7] 38.2 [22.7] 3
0 1 2
2
7/2 40.9 [15.1] 37.4 [22.2] 7
7 0 0
0
3/0 29.3 [6.8] 26.3 [15.8] 1
0 1 0
0
2/0 50 [5.7] 70 [1.4] 1
0 1 0
0
0/1 45 [-] 62 [-] 1
0 1 0
0
Spontaneous bleeding,2 n. of patients WHOgrade=1,n. 7 WHOgrade=2,n. 4 WHOgrade=3,n. 2
Previous splenectomy,3 n. of patients 2
1As evaluated by phase-contrast microscopy in a counting chamber. 2Spontaneous bleeding during the week preceding the baseline evaluation according to the World Health Organization bleeding scale. 3Previous splenectomy because of a mistaken diagnosis of immune thrombocytopenia. MYH9-RD: MYH9-related disease; ANKRD26-RT: ANKRD26- related thrombocytopenia; XLT/WAS: X-linked thrombocytopenia/Wiskott-Aldrich syndrome; mBSS: monoallelic Bernard-Soulier syndrome; ITGB3-RT: ITGB3-related thrombocy- topenia; n: number; M: male; F: female; SD: standard deviation; WHO: World Health Organization.
Table 2. Responses in part 1 of the study (primary endpoint), overall and according to the different forms of inherited thrombocytopenia.
Evaluable patients, n.
Response1
Any response, % [95% CI]
Major response, % [95% CI]
Minor response, % [95% CI]
Platelet count2
Baseline, x109/L, mean [SD]
End of part 1, x109/L, mean [SD]
Mean increase, x109/L [95% CI]
Mean increase in responders,
x109/L [95%CI]
Spontaneous bleeding3
Patients with SB at baseline, n.
Complete remission of SB at end
of part 1, % [95% CI]
Partial reduction of SB at end
of part 1, % [95% CI]
Overall
23
91.3 [72.0-98.9]
47.8
[26.8-69.4]
43.5 [23.2-65.5]
40.4 [22.8] 104.9 [56.7]§ 64.5 [43.7-85.3] 69.5 [48.0-91.1]
12
83.3 [51.6-97.9]
8.3 [0.2-38.5]
MYH9-RD 9
100.0 [66.4-100.0]
77.8
[40.0-97.2]
22.2 [2.8-60.0]
38.2 [22.7] 136.3 [68.0]# 98.1 [53.3-142.9] 98.1 [53.3-142.9]
3
100 [29.2-100]
0 [0.0-70.8]
ANKRD26-RT 8
87.5 [47.3-99.7]
25.0
[3.2-65.1]
62.5 [24.5-91.5]
38.0 [23.7] 75.5 [28.5]§ 37.5 [24.1-50.8] 41.8 [31.7-52.0]
6
83.3 [35.9-99.6]
0 [0.0-45.9]
WAS/XLT
3
100.0 [29.2-100.0]
0
[0-70.8]
100.0 [29.2-100.0]
26.3 [15.8]
67.7 [38.4] 41.4 [22.1-104.8] 41.4 [22.1-104.8]
1
100 [2.5-100]
0 [0.0-97.5]
mBSS
2
100.0 [15.8-100.0]
100.0
[15.8-100.0]
0 [0-84.2]
70.0 [1.4] 150.5 [13.4] 80.5 [27.5-188.5] 80.5 [27.5-188.5]
1
100 [2.5-100]
0 [0.0-97.5]
ITGB3-RT 1
0 [0-97.5]
0
[0-97.5]
0 [0-97.5]
62.0 [-] 78.0 [-] 16.0 [-] -
1
0 [0-97.5]
100 [2.5-100]
1According to predefined study criteria. 2As evaluated by phase-contrast microscopy in a counting chamber. 3Spontaneous bleeding during the week preceding evaluation according to the World Health Organization bleeding scale. §P<0.001 with respect to baseline. #P=0.001 with respect to baseline. MYH9-RD: MYH9-related disease; ANKRD26-RT: ANKRD26-related thrombocytopenia; XLT/WAS: X-linked thrombocytopenia/Wiskott-Aldrich syndrome; mBSS: monoallelic Bernard-Soulier syndrome; ITGB3-RT: ITGB3-related thrombocytopenia; n: number; 95% CI: 95% confidence interval; SD: standard deviation; SB: spontaneous bleeding..
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