Page 309 - Haematologica March 2020

Eltrombopag in inherited thrombocytopenias
was 64.5x109/L (95% CI: 43.7-85.3) overall, and 69.5x109/L in the 21 responders. Table 2 and Figure 1 report the average increase in platelet count in the respon- ders according to the different forms of inherited throm- bocytopenia.
Ten of the 12 patients with spontaneous bleeding at baseline (83.3%) obtained complete remission of bleed- ing. In particular, all responders (major or minor response) achieved disappearance of bleeding symptoms if present at baseline. Of the two non-responders, the patient with ANKRD26-RT did not obtain any improvement of bleed- ing manifestations, whereas the patient with ITGB3-RT experienced a reduction of spontaneous bleeding (WHO grade from 2 to 1) following a slight increase in platelet count (from 62 to 78 x109/L).
Table 3. Doses of eltrombopag administered during part 1 of the study.
Eltrombopagdose
Ten patients (43.5%) achieved a major response with eltrombopag 50 mg/day and stopped therapy (Table 3). These patients were all the individuals with MYH9-RD or mBSS who obtained a major response and one subject with ANKRD26-RT. Thus, 13 patients (56.5%) switched to the dosage of 75 mg/day. Treatment with the higher dose resulted in the achievement of a better response according to the study criteria in four of these subjects (Table 3).
Exploratory endpoints
In vitro platelet aggregation in response to collagen, ADP, and ristocetin, was studied at the end of treatment in the 11 patients who achieved platelet counts >100x109/L.
Evaluable patients, n.
Major response with 50 mg/day, n. (%)
Switch to 75 mg/day, n. (%)
Improvement of response with 75 mg/day1, n.
Overall
23
10 (43.5)
13 (56.5)
4
MYH9-RD 9
7 (77.8)
2 (22.2)
0
ANKRD26-RT 8
1 (12.5)
7 (87.5)
2§
WAS/XLT
3
0
3 (100)
2#
ITGB3-RT 2 1
2 (100) 0
0 1
0 0
mBSS
1Achievement of a better response according to the study criteria with respect to treatment with 50 mg/day. §One patient achieved a major response, one achieved a minor response. #Both patients achieved minor responses. 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.
Figure 1. Mean increase in platelet count in the respon- ders in part 1 of the study.
Patients are
according to the diagnosis of the specific form of inherited thrombocytopenia. mBSS: monoallelic Bernard-Soulier syndrome; MYH9-RD: MYH9- related disease; . ANKRD26-RT: ANKRD26-related thrombocy- topenia. XLT/WAS: X-linked thrombocytopenia/Wiskott- Aldrich syndrome. Mean values of platelet count at baseline and at the end of part 1 of the treatment along with their 95% confidence intervals (95%CI) are reported in the gray box.
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