Eltrombopag is an oral thrombopoietin (TPO) receptor agonist that has previously been shown to be effective in patients with aplastic anemia (AA) both in frontline and salvage setting.1,2 Yet, its efficacy has thus far been limited to clinical trials, and its application in real-world clinical practice remains elusive.3 Now, this missing piece of information is filled by the University of Hong Kong (HKU) Hematology Team, and the study was published in Hematology.3
AA is a rare disorder characterized by pancytopenia with a hypocellular bone marrow.2 Patients could be cured by hematopoietic stem-cell transplantation, but immunosuppressive therapy (IST) alone is also effective, with around 70% of patients reporting increased blood-cell production after treatment with horse anti-thymocyte globulin (ATG) and cyclosporine.2,3 Many efforts to further improve the standard treatment have failed, with reasons possibly attributing to stem-cell deficit.2
It has been postulated that eltrombopag may overcome this limitation by mediating stimulation or expansion of the remaining stem cell pool in the bone marrow.4 While eltrombopag has been consistently reported to be efficacious in both refractory severe AA or treatment-naïve patients, its efficacy in non-trial setting remains to be defined.1-3 Dr. Yu-Yan Hwang and colleagues provided the first piece of evidence to evaluate the use of eltrombopag in AA patients in a routine hematological practice.3
In this study, 20 consecutive AA patients (newly diagnosed: n=10; relapsed/refractory: n=10) treated with eltrombopag within the 4.5-year study period were analysed.3 All patients were required to have eltrombopag administered for at least 12 weeks (the first time-point of assessment of response) in order to be eligible for the analysis.3
For newly diagnosed patients, three eltrombopag regimens were used: in combination with ATG and cyclosporin (n=4), in combination with cyclosporin only (n=5), and as monotherapy (n=1), with a median maximum dose of 150 (50–300)mg/day.3
The responses were very favorable with an overall response rate (ORR) of 90%, and trilineage response of 60%.3 “This real-life clinical experience showed interesting features,” the researchers wrote, firstly, consistent with previous reports, “[our findings] suggested that both the timing of treatment initiation and the total duration of exposure to eltrombopag have impacts on treatment response… [that is] early addition of eltrombopag to AA treatment would be beneficial,” they explained.3 “Furthermore, although ATG is widely considered to be the standard first-line treatment, it is apparently not mandatory for eltrombopag to be effective.”3
As for relapsed/refractory patients, eltrombopag was used alone, also at a median maximum dose of 150 (50–300)mg/day, although continuation of previous cyclosporin therapy was allowed in some patients.3
The ORR was reported to be 50%, with trilineage response of 40%.3 “[This] was remarkable given that these patients had failed multiple courses of ATG and cyclosporin,” the researchers noted. 3 However, whether the response can be maintained once eltrombopag is tapered off remains to be determined.3
While the efficacy of eltrombopag in everyday practice was comparable to those reported in trials, the dose used in this real-world study was notably higher.3 Due to a lower eltrombopag clearance rate in Asian population, this agent generally delivered a starting dose 50% lower as compared to other populations.3 “In previous phase 1/2 studies of eltrombopag in predominantly non-Asian AA patients, the ceiling dose of eltrombopag has been set at 150mg/day… In our patients, however, we have used eltrombopag in doses of which could be equivalent to a maximum of 450mg/day and [a median of] 225mg/day in non-Asian patients,” they wrote, “it remains uncertain if such high doses were actually required to obtain responses in our patients. However, serious toxicities were not observed, suggesting that eltrombopag could be used in doses higher than those previously reported.”3 The most common adverse effect was skin pigmentation, which was fully reversible on cessation of eltrombopag treatment.3
Simply put, data from this real-world study revealed that eltrombopag is an efficacious, feasible, and safe therapeutic option to AA patients both in frontline and salvage setting.3
1. Olnes MJ, Scheinberg P, Calvo KR, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012;367(1):11–19.
2. Townsley DM, Scheinberg P, Winkler T, et al. Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med. 2017;376(16):1540–1550.
3. Hwang YY, Gill H, Chan TSY, et al. Eltrombopag in the management of aplastic anaemia: real-world experience in a non-trial setting. Hematology. 2018 [Epub ahead of print].
4. Rodeghiero F, Carli G. Beyond immune thrombocytopenia: the evolving role of thrombopoietin receptor agonists. Ann Hematol. 2017;96(9):1421-1434.