Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia

Abstract

Background Acquired aplastic anemia results from immune-mediated destruction of bone marrow. Immunosuppressive therapies are effective, but reduced numbers of residual stem cells may limit their efficacy. In patients with aplastic anemia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist, led to clinically significant increases in blood counts in almost half the patients. We combined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe aplastic anemia. Methods We enrolled 92 consecutive patients in a prospective phase 1–2 study of immunosuppressive therapy plus eltrombopag. The three consecutively enrolled cohorts differed with regard to the timing of initiation and the duration of the eltrombopag regimen (cohort 1 received eltrombopag from day 14 to 6 months, cohort 2 from day 14 to 3 months, and cohort 3 from day 1 to 6 months). The cohorts were analyzed separately. The primary outcome was complete hematologic response at 6 months. Secondary end points included overall response, survival, relapse, and clonal evolution to myeloid cancer. Results The rate of complete response at 6 months was 33% in cohort 1, 26% in cohort 2, and 58% in cohort 3. The overall response rates at 6 months were 80%, 87%, and 94%, respectively. The complete and overall response rates in the combined cohorts were higher than in our historical cohort, in which the rate of complete response was 10% and the overall response rate was 66%. At a median follow-up of 2 years, the survival rate was 97%; one patient died during the study from a nonhematologic cause. Marked increases in bone marrow cellularity, CD34+ cell number, and frequency of early hematopoietic progenitors were noted. Rates of relapse and clonal evolution were similar to our historical experience. Severe rashes occurred in two patients, resulting in the early discontinuation of eltrombopag. Conclusions The addition of eltrombopag to immunosuppressive therapy was associated with markedly higher rates of hematologic response among patients with severe aplastic anemia than in a historical cohort. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT01623167.)

How I treat acquired aplastic anemia

“…71 The overall response at 6 months was 85%, with survival on the order of 90%. Cytogenetic abnormalities and clonal evolution to myelodysplasia occurred at a similar frequency compared with standard IST, although follow-up is still short.…”

“…Cytogenetic abnormalities and clonal evolution to myelodysplasia occurred at a similar frequency compared with standard IST, although follow-up is still short. 71 The EBMT Working Party for Severe Aplastic Anemia is running 2 prospective randomized studies: 1 compares ATG1CsA with or without EPAG in SAA, and the other compares CsA with or without EPAG in non-SAA. For personal use only.…”

Eltrombopag for use in children with immune thrombocytopenia

“…In a study of 92 pediatric and adult patients with severe AA refractory to immunosuppression, the addition of eltrombopag resulted in increased bone marrow cellularity and the frequency of hematopoietic progenitor cells. 42 Platelet counts improved at 3 and 6 months when treatment consisted of standard immunosuppression and eltrombopag was compared with treatment for historical controls. 42 Patient's absolute neutrophil counts also improved at these time points, and red blood cell transfusion independence was achieved at a median of 32 days.…”

An update on Acquired Aplastic Anemia

“…No increase in clonal evolution was observed with Eltrombopag compared to immune suppression [15]. Last year the results of a trial using Eltrombopag upfront in treatment-naive aplastic anemia patients were published; when Eltrombopag is used upfront with antithymocyte globulin and cyclosporine a response rate of 95% was observed [16]. Clinical trials are ongoing in Europe and in the United States using Eltrombopag upfront with immune suppression and the results so far show that Eltrombopag will be the new player in the first line treatment in aplastic anemia patients.…”