Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia

Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia
For pediatric patients with a diagnosis of Aplastic Anemia and without matched-related donor, immune suppressive treatment (IST) is the treatment of choice and leads to an initial response in about 2/3 of patients with about 1/3 of initial responders relapsing over time and 10-20% developing clonal evolution. This article addresses the question whether addition of eltrombopag, an oral thrombopoietin-receptor agonist leads to an increase in response to IST. Eltrombopag was previously shown to lead to a response in a subset of IST-refractory patients with aplastic anemia, particularly in those with a higher reticulocyte count. The authors are among the most established people performing research on aplastic anemia and are affiliated to the NIH.
This is a phase I/II study with 92 patients divided into three groups with varying timing of addition of eltrombopag: either from day 14 to 6 months, from day 14 to 3 months, or from day 1 to 6 months after IST (cohorts 1, 2, and 3 respectively). The main outcome was complete response (CR) after 6 months.
In this trial, the best results were seen in the group starting eltrombopag with IST and continuing to 6 months (cohort 3) with 58% CR and 94% overall response (OR). The other treatment groups led to CR of 33% and 26% (87% and 80% OR) in cohort 1 and cohort 2, respectively. This is far better than what was seen in the historical controls used in this trial with 10% CR and 66% OR.
A major limitation to this trial was that there were only historical controls and no direct comparison group without eltrombopag. The retic counts in the eltrombopag group were slightly higher compared to controls which might point towards a “milder” disease. The whole cohort consisted of a mixed group of adults and kids with a wide age range (3-82 years). Finally, there was an amendment in the middle of the study period extending the time of cyclosporine A treatment from 6 months to 24 months adding further uncertainty what caused the better response in cohort 3 which was treated last.
Eltrombopag was shown to increase response rate in a mixed cohort of pediatric and adult patients when being added to IST upfront together with a prolonged duration of cyclosporine A treatment of 24 months. While these results are very promising, further data will be needed from pediatric cohorts.