Outcome of Standard Immunosuppressive Therapy with or without Eltrombopag for Chinese Patients with Severe Aplastic Anemia in the Real World

BACKGROUND

Immunosuppression is the current standard therapy for patients with severe aplastic anemia(SAA), whereas allogeneic haematopoietic stem cell transplantation (HSCT) is recommended for patients younger than 50 years old, if donors are available. Immunosuppression with antithymocyte globulin (ATG) and ciclosporin results in an overall response rate (ORR) of about 70%. In Chinese SAA patients, porcine ATG and rabbit ATG resulted apparently in similar ORRs and survivals. The low CR rate of immunosuppression with ATG suggests that other strategies are needed to improve outcome. Eltrombopag is an oral thrombopoietin receptor agonist. In a recent study of newly diagnosed SAA patients, combined standard immunosuppressive therapy (IST) with eltrombopag, the patients in one of three cohorts who received eltrombopag from day 1 to 6 months achieved higher ORR at 6 months (94%) and CR rate(58%). The results showed a higher rate of treatment response than in the past. But the data of eltrombopag in SAA have so far been limited to clinical trials, and its efficacy in routine practice remains undefined, especially for Chinese SAA patients. Recently, we retrospectively analyzed the results of 48 cases suffer from SAA received standard immunotherapy combined with or without eltrombopag in our center, so as to explore the effects and adverse reactions in the real world.

METHODS

48 consecutive newly diagnosed patients with severe aplastic anemia were enrolled in this study. Out of 48 cases, 27 were male, and 21 were female. The median age was 46 years old (ranged from 18 to 69 years old). SAA patients who received ATG combined with cyclosporine A (CsA) therapy with or without eltrombopag were analysed retrospectively. The patients were divided into a eltrombopag group (n = 14) and a without eltrombopag group (n = 34). The eltrombopag group received eltrombopag (median daily dose 75 mg) from the beginning of IST and for at least 3 months. The primary outcome was complete hematologic response at 6 months. At the same time, overall response, survival, relapse, and clonal evolution to myeloid cancer were observed.

RESULTS

After three months, the eltrombopag group and without eltrombopag group had an ORR of 69.5% and 47.2%, respectively (P = 0.063); after six months, the ORR reached 85.7% and 73.6%, respectively (P = 0.078). The rates of complete response at 6 months was 35.7% in the eltrombopag group and 29.4% in without eltrombopag group. The complete and overall response rates in the eltrombopag group were higher than in without eltrombopag group. However, due to the small number of cases, there was no statistical difference. At a median follow-up of 2 years, the survival rate was 97.9%; one patient died from a hematologic cause. Rates of relapse and clonal evolution were similar in two gruops. Adverse effects included reversible rashes, dyspepsia, and liver function derangement.

CONCLUSIONS

Rates of hematologic response among chinese patients with severe aplastic anemia treated with standard immunosuppressive therapy plus eltrombopag was markedly higher than without eltrombopag.

【Key words】

Aplastic anaemia; newly diagnosed; eltrombopag; antithymocyte globulin;