Page 182 - 2019_11 Resto del Mondo-web
P. 182

M.D. Tarantino et al.
comes such as ITP duration, past ITP treatments, and platelet counts in the first four weeks on study were eval- uated for their ability to predict treatment-free response. In the univariate model, younger age at diagnosis, younger age at first dose, platelets >200x109/L in the first four weeks, and higher mean platelet count in the first four weeks were each associated with developing a treatment- free response (Table 5). In the multivariate model, age at first dose (P=0.0012) and platelet counts >200x109/L in the first four weeks (P=0.0035) continued to correlate with treatment-free response (Figure 3B).
Discussion
The data from up to seven years of treatment in this open-label extension study in children with ITP demon- strated that romiplostim was well tolerated and generally maintained its efficacy. There were no complications of thrombotic events, fatalities, or new safety concerns, despite 182 patient-years of exposure to romiplostim (>200 patient-years including parent studies) in 65 patients, half of whom were 11 years of age or less at study baseline. Approximately one-third of patients had serious AE in this trial in which patients were on study for a median of 2.6 years, but only one patient had an episode of concurrent treatment-related serious AE: thrombocy- topenia, epistaxis, and anemia. One patient developed neutralizing anti-romiplostim antibodies, discovered when she discontinued the study due to needing other treatments, but neither she nor any other patient devel- oped neutralizing antibody to TPO. This finding in 1 of 60 children is consistent with data from adults treated with romiplostim for ITP. In an integrated database of romi- plostim ITP trials, anti-romiplostim neutralizing antibod- ies were found in 4 of 1,046 adult patients with a total exposure of 1,832 patient-years.12
The most common reasons for discontinuation of study
treatment were withdrawal of consent (n=10) and required alternative therapy (n=5). Over 90% of patients had a peak platelet count of >50x109/L without rescue medication at least once and approximately three-quarters of patients had ≥75% of their platelet counts >50x109/L, suggesting a very high rate of efficacy of romiplostim in these children with chronic ITP with a median ITP dura- tion of three years at the start of therapy. Furthermore, median platelet counts were maintained in the desired range (50-200x109/L) from week 2 on and at >100x109/L from weeks 24 to 260 despite a median dose of 4-5 mg/kg, the same median dose as in the phase III study.10
Overall, 15 of 65 children (23%) achieved a treatment- free response, which was defined as platelet counts of ≥50x109/L for at least 24 weeks while withholding romi-
Table 3. Adverse events.
Category AE
Most common AE Headache Contusion Epistaxis
Upper respiratory tract infection
Most common serious AE† Any
Thrombocytopenia Pyrexia
Epistaxis Headache Vomiting
Duration-adjusted events per 100 pt-yr
Patient incidence All treated patients N=65 n (%)
All treated patients 182 pt-yr # (rate)
151 (83) 435 (239) 103 (57) 101 (56)
54 (30) 6 (3)
3 (2)
2 (1)
2 (1)
2 (1)
Excluding 1 patient with 499 AE* 178 pt-yr
# (rate)
126 (71) 164 (92) 98 (55) 101 (57)
41 (23) 6 (3) 3 (2) 2 (1) 1 (0.6) 1 (0.6)
38 (59) 33 (51) 32 (49) 32 (49)
19 (29) 4 (6) 3 (5) 2 (3) 2 (3) 2 (3)
Table 4. Patients achieving treatment-free response (defined as a treatment-free period of ≥24 weeks with platelet counts ≥50x109/L).
AE: adverse event; pt-yr: patient-years. *See text for a description of the AE in this patient. †A full list of serious AE is provided in Online Supplementary Table S1.
Parent study
Patientnumber
Ageattreatment-free
response start, y
Phase I/II Phase III
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
16 6 10 8 6 12 18 7 6 9 4 5 6 16 14
Sex FMMFFFFMMFMFFMF
Race/ethnicity WBW WWWWWBAWBHWW
Parent study treatment Rom Rom Rom Rom Rom Rom Pbo Rom Rom Pbo Pbo Pbo Rom Rom Rom
Baselineplateletcount,x109/L* 12 5 9 18 7 44 15 26 28 28 25 1 11 4 14
NumberofpastITPtherapies* 3 6 4 2 2 3 4 5 2 1 2 1 4 3 4
ITPduration,years† 7 6 5 1 4 11 12 3 1 2 3 4 3 3 5
Rituximabuse,years† 455 –––––––––2–5
Romiplostimuse,years† 765235433222313
Maximumromiplostim 10 8 9 5 10 2 2 1 3 1 2 1 9 10 4 dose, mg/kg
ITP treatment-free 1.1 2.1 1.1 1.6 1.0 0.8 0.9 1.7 2.1 1.1 0.6‡ 0.6 0.8 0.4§ 0.6
response, year
Data are integrated over parent study and extension study. –: no rituximab use; A: Asian; B: black; F: female; H: Hispanic/Latino; ITP: immune thrombocytopenia; M: male; Pbo: placebo; Rom: romiplostim;W:white.*At start of parent study.†Before treatment-free response.‡Treatment-free response ended before study end.§This patient met treatment-free response criteria for 0.4 years on study and ≥0.5 years post-study.
2288
haematologica | 2019; 104(11)


































































































   180   181   182   183   184