Page 105 - 2019_05-HaematologicaMondo-web

EXPAND: 48-week follow-up analysis
Efficacy in the maximum safe starting dose cohort
Spleen response. At week 48, spleen response was achieved in 5 out of 15 patients [33.3% (95%CI: 11.8, 61.6)] in S1 and 3 out of 10 patients [30.0% (95%CI: 6.7, 65.2)] in S2. A spleen response at any time point was observed in 8 out of 20 patients [40.0% (95%CI: 19.1, 63.9)] in S1 and 12 out of 18 patients [66.7%
(95%CI: 41.0, 86.7)] in S2 (Figure 4).
The waterfall plot for the best response in spleen length for
patients treated at the MSSD, with or without dose titration, within the first 12 weeks is presented in Online Supplementary Figure S2. A decrease in best percentage change from baseline in spleen length was evident in 100.0% of patients with dose down-
Table 2. All grade adverse events, regardless of study drug relationship, in ≥15% of patients in either stratum (week 48 analysis; maximum safe starting dose cohort).
Preferred term
Anemia
Thrombocytopenia
Platelet count decreased
Pyrexia
Abdominal pain
Diarrhea
Ecchymosis
Epistaxis
White blood cell count decreased
Back pain
Blood bilirubin increased
Alanine aminotransferase increased
Aspartate aminotransferase increased
Asthenia
Fatigue
Neutrophil count decreased
Cough
Hypocalcemia
Nasopharyngitis
Headache
Hypertension
Nausea
Leukocytosis
Peripheral edema
Pain in extremity
Vomiting
AE: adverse event; MSSD: maximum safe starting dose.
Stratum 1 (N=20) Stratum 2 (N=18)
All grades Grade 3 or 4 All grades Grade 3 or 4
N(%) N(%) N(%) N(%)
9 (45.0)
8 (40.0) 6 (30.0) 6 (30.0) 5 (25.0) 5 (25.0) 5 (25.0) 5(25.0) 5 (25.0) 4 (20.0) 4 (20.0) 3 (15.0) 3 (15.0) 3 (15.0) 3 (15.0) 3 (15.0)
4 (20.0)
7 (35.0) 5 (25.0) 0
0
1 (5.0) 0
8 (44.4) 3 (16.7)
14 (77.8) 14 (77.8) 00
4 (22.2) 4 (22.2) 5 (27.8) 2 (11.1)
1 (5.6) 0
0
0
0
0
0
0
1 (5.6) 0
2 (11.1) 0
0
0
0
0
0
0
0
1 (5.6) 0
0
0
0 0
2 (10.0) 0
2 (10.0) 1 (5.0) 1 (5.0) 1 (5.0) 1 (5.0) 1 (5.0)
1 (5.6) 2 (11.1) 1 (5.6) 1 (5.6) 1 (5.6) 5 (27.8) 3 (16.7) 0
0 0 6(33.3)
2 (10.0) 2 (10.0) 1 (5.0) 1 (5.0) 1 (5.0) 1 (5.0) 1 (5.0) 0
1 (5.0)
0
0
0
1 (5.0) 0
1 (5.0) 1 (5.0) 0
0
5 (27.8) 5 (27.8) 4 (22.2) 4 (22.2) 4 (22.2) 3 (16.7) 3 (16.7) 3 (16.7) 3 (16.7)
Figure 3. Mean daily dose over time by stratum at maximum safe starting dose. bid: twice daily.
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