Activity of eltrombopag in severe aplastic anemia

Abstract

Since the approval of horse antithymocyte globulin (ATG) decades ago, there was a long hiatus in therapies with activity in severe aplastic anemia (SAA). This scenario changed in 2014 when eltrombopag, a thrombopoietin receptor agonist, was approved for SAA after an insufficient response to initial immunosuppressive therapy (IST). The basis for this approval was the observation of single-agent activity of eltrombopag in this patient population, where 40% to 50% recovered blood counts at times involving >1 lineage. The achievement of transfusion independence confirmed the clinical benefit of this approach. Increase in marrow cellularity and CD34+ cells suggested a recovery to a more functioning bone marrow. Further in its development, eltrombopag was associated with standard horse ATG plus cyclosporine in first line, producing increases in overall (at about 90%) and complete response rates (at about 40%) and leading to transfusion independence and excellent survival. Interestingly, best results were observed when all drugs were started simultaneously. The cumulative incidence of clonal cytogenetic abnormalities to date has compared favorably with the vast experience with IST alone in SAA. Longer follow-up will help in define these long-term risks. In this review, the development of eltrombopag in SAA will be discussed.

Effectiveness and safety of tacrolimus with or without eltrombopag, as a part of immunosuppressive treatment of aplastic anemia in adults: a retrospective case series

“…Eltrombopag plus standard IST using horse ATG and CsA has been demonstrated to improve blood counts and efficacy of the IST in the setting of refractory aplastic anemia. However it's use in combination with tacrolimus has never been described [1,25,26]. In our study, most of the patients treated with any line tacrolimus received concurrent eltrombopag.…”

Pure red cell aplasia and amegakaryocytic thrombocytopenia in thymoma: The uncharted territory

“…Eltrombopag has been used, beside our patient, in only one case but no improvement of platelet count was obtained; at the end a bone marrow, transplant from matched unrelated donor was successfully performed . Our case is an example where the addition of a TPO agonist did not provide an hematological recovery, whereas in the latest years this molecule has been proven effective in the treatment of severe aplastic anemia (SAA) both as a single agent in SAA refractory to IST or in frontline combination with cyclosporine/horse ATG …”

Correlation of the Plasma Concentration of Eltrombopag With Efficacy in the Treatment of Refractory Aplastic Anemia: A Single-Centre Study in China

“…Elevated transaminase is the most common dose-dependent toxic effect of ELT (Ecsedi et al, 2019), according to published data. Other side effects mentioned in the literature include skin rash, elevated bilirubin, skin pigmentation, nausea, fatigue, cough, diarrhea, headache, and possible clone evolution (Lum and Grainger, 2016;Scheinberg, 2019). In a recent study in Europe, ADRs were reported in 28% (51/180) of patients (Ecsedi et al, 2019).…”