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M.D. Tarantino et al.
first such report of children entering treatment-free response after treatment with a TPO receptor agonist, although this has been observed in adults.28-30
Only 2 of 66 patients discontinued romiplostim due to AE. However, investigators reported that 42% (28 of 66) of patients stopped romiplostim treatment early. It is unknown how many of these patients changed to com- mercially available romiplostim to avoid the constraints of protocol-required study visits. The withdrawal rate is comparable to the romiplostim ITP extension study in adults (31% withdrawal rate in a 7-year study)31 and the eltrombopag ITP extension study in adults (55% in an 8- year study).32
The lack of a control group in this study limits the inter- pretation of the results. However, even without a control group, the low number of treatment-related serious AE, lack of new types of AE, and the absence of bone marrow or thromboembolic findings are reassuring. The international nature of this study may have increased the degree of patient and previous treatment heterogeneity but at the
A
same time increased generalizability of the results. The requirement for regular clinic visits and platelet count meas- urements/dose modifications could have presented a deter- rent both for patients to enter and to continue the study; dose modifications required weekly visits again for a short period. A number of children left the study without obvious explanation, suggesting that even when self-administration is an option, a few patients will discontinue treatment despite responding, and are not leaving due to AE or loss of treatment effect. There were no quality-of-life assessments, which could also have indicated how increased platelet counts and decreased use of other ITP medications, and also the requirements of the study itself, affected quality of life.
In conclusion, romiplostim was a highly successful maintenance therapy even in children with ITP ≥6 months’ duration not responsive to other therapies, a majority of whom (62%) had received three or more past ITP treatments. Romiplostim treatment demonstrated consistent safety and efficacy over the course of this long-term study. Patients staying on study were able to
B
Figure 3. Treatment-free response for at least six months. Shown are time to onset (A) and modeling of characteris- tics associated with treatment-free response (B). If, in the opinion of the investigator, the patient maintained acceptable platelet counts without weekly dosing, romiplostim could be withheld until the platelet count fell to <50x109/L. If the platelet count was >200 to <400x109/L for two consecu- tive weeks, the dose was reduced by 1 mg/kg at the next scheduled dose. If the platelet count was ≥400x109/L, the dose was withheld and reduced on the next scheduled day of dosing when the platelet count was <200x109/L. Red boxes indicate factors significant in the univariate analyses; yellow high- lighting indicates those significant in the multivariate analyses. Hazard ratios for age at first dose and age at immune thrombocytopenia (ITP) diag- nosis are per year of age, the hazard ratio for baseline platelet count is per 1x109/L, and the hazard ratio for mean platelet count in the first four weeks is per 10x109/L. Hazard ratios greater than 1 indicate an increased likelihood of developing treatment-free response. Note: the univariate models for prior rituximab use (P=1.0) and prior splenectomy (P=0.32) had non-propor- tional hazards, hence neither factor has a hazard ratio. #: number of; meds: medications.
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haematologica | 2019; 104(11)