Long-term results of a phase 2 trial involving patients with severe aplastic anemia (SAA) suggest that treatment with eltrombopag (EPAG) and immunosuppression (IST) may not reduce the risk of relapse and clonal evolution, compared with treatment using IST without EPAG. The study results were published in the journal Blood.

The report was a secondary endpoint analysis of the phase 2 trial (ClinicalTrials.gov Identifier: NCT01623167), in which the combination of IST and EPAG (EPAG-IST) had earlier been associated with improved hematologic response when compared with a historical cohort treated only with IST. All patients given EPAG-IST also received horse antithymocyte globulin (hATG) and cyclosporine (CSA), and those in the historical IST-treated cohort received horse or rabbit ATG and CSA.

Patients treated with EPAG-IST were divided into 3 cohorts based on administration of EPAG, which was given to cohort 1 from day 15 to 6 months, to cohort 2 from day 1 to 3 months, and to cohort 3 from day 1 to 6 months. Cohort 1 consisted of 30 patients, cohort 2 had 31 patients, and cohort 3 had 117 patients. Cohort 3 was larger than other EPAG-IST cohorts because it included patients who entered into extension analysis. The historical IST-treated cohort had 102 patients. The current analysis involved a median follow-up of 4 years since the earlier analysis.

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The 6-month overall response rate with EPAG-IST was 81%, compared with 67% for the historical IST-treated cohort (P =.008). Among patients responding to EPAG-IST by 6 months, 61 patients had relapses. The median 4-year cumulative incidence of relapse was 43%. Relapses usually occurred either when EPAG was stopped and the CSA dose was reduced, or later with the completion of CSA maintenance.

When relapse rates were analyzed in patients receiving EPAG-IST with CSA maintenance of a similar duration to that of the historical cohort, the 4-year cumulative relapse rate was 39% with EPAG-IST, compared with 33% for the historical IST-treated group (P =.09). In this comparison, patients given EPAG-IST had a median time to relapse of 324 days, while the historical cohort had a median time to relapse of 774 days.

High-risk clonal evolution occurred at a rate of 5.7% with EPAG-IST and at a rate of 10.3% in the historical IST-treated group (P =.5). Clonal evolution overall occurred with a 4-year cumulative incidence of 15% with EPAG-IST, which was reportedly similar to the rate for the historical cohort. When clonal evolution occurred, the median time to the event was 186 days with EPAG-IST and 777 days with IST only. The 4-year overall survival rates were 92.5% with EPAG-IST and 85% for the historical IST-treated cohort (P =.41).

“With no increase in the rates of clonal evolution, the combination of IST and EPAG should be used as first-line treatment in adult SAA patients who do not have safe transplant options,” the study investigators concluded in their report. However, they also noted that “durability of response remains inadequate in many treated patients, demanding a focus on optimizing therapies with longer-term benefits.”

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Patel BA, Groarke EM, Lotter J, et al. Long-term outcomes in patients with severe aplastic anemia treated with immunosuppression and eltrombopag: a phase 2 study. Blood. 2022;139(1):34-43. doi:10.1182/blood.2021012130