Long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag: a phase 2 study

Abstract

Patients with severe aplastic anemia (SAA) are either treated with bone marrow transplant (BMT) or immunosuppression (IST) depending on their age, comorbidities, and available donors. In 2017, our phase 2 trial reported improved hematologic responses with the addition of eltrombopag (EPAG) to standard IST for SAA when compared to a historical cohort treated with IST alone. However, the rates and characteristics of long-term complications, relapse, and clonal evolution, previously described in patients treated with IST alone are not yet known with this new regimen, IST and EPAG. Patients were accrued from 2012 to 2020 with a total of 178 subjects included in this secondary endpoint analysis. With double the sample size and a much longer median follow-up (4 years) since the original report in 2017, we report a cumulative relapse rate of 39% in responding patients who received CSA maintenance, and clonal evolution of 15% in all treated patients at 4 years. Relapse occurred at distinct timepoints: after cyclosporine dose reduction and EPAG discontinuation at six months, and after two years when cyclosporine was discontinued. Most relapsed patients were retreated with therapeutic doses of cyclosporine +/- EPAG, and two-thirds responded. Clonal evolution to a myeloid malignancy or chromosome 7 abnormality (high-risk) was noted in 5.7% of patients and conferred a poorer overall survival. Neither relapse nor high-risk evolution occurred at a higher rate than was observed in a historical comparator cohort but the median time to both events were earlier in IST and EPAG treated patients. Trial registered in clinicaltrials.gov (NCT01623167).

Association between human leukocyte antigen and immunosuppressive treatment outcomes in Chinese patients with aplastic anemia

“…Since age and disease severity were independent predictors of response to IST and clonal evolution in AA patients ( 21 – 24 ), patients were further subdivided into three groups according to age (<18 years old, ≥18 and <40 years old, ≥40 years old) and two groups (VSAA and SAA) according to the disease severity.…”

Hetrombopag plus porcine ATG and cyclosporine for the treatment of aplastic anaemia: early outcomes of a prospective pilot study

“…The National Institutes of Health study showed a cumulative relapse rate of 39% in patients with SAA treated with IST plus EPAG, compared to IST alone [ 11 ]. Herein, two patients experienced relapse which may be associated with dose tapering of cyclosporine and HPAG.…”

Comparison of hematopoietic stem cell transplantation and immunosuppressive therapy as the first-line treatment option for patients with severe hepatitis−associated aplastic anemia

“…Unfortunately, TPO-RAs was not available in China until 2019 thus patients in our study did not receive TPO-RA therapy. Moreover, the high incidence of hepatotoxicity following eltrombopag-IST requires extra caution (36). In contrast, the reduced hepatotoxicity of hetrombopag makes it a better candidate for combinational use with IST for HAAA though liver function should be closely monitored.…”