Eltrombopag and Cyclosporin A Demonstrate Beneficial Outcomes as Frontline Treatment for Patients With Severe Aplastic Anemia

Findings from the Phase 2 SOAR Trial

According to findings from the phase 2 SOAR trial published in The Lancet Haematology, eltrombopag plus cyclosporin A demonstrated activity and beneficial outcomes, including a lack of new safety symbols, as a frontline treatment for patients with severe aplastic anemia who were unable to access or tolerate horse-antithymocyte globulin (ATG). 

Phillip Scheinberg, MD, PhD, Hospital A Beneficência Portuguesa, São Paulo, Brazil, and coauthors explained that although ATG-based immunosuppression is commonly used as a standard frontline treatment among patients with severe aplastic anemia without a histocompatible donor or who are 40 years or older, the treatment “requires in-hospital administration, is associated with infusion-related toxicities and has limited availability worldwide.” 

The study authors aimed to assess the potential value of eltrombopag plus cyclosporin A, an ATG-free regimen, among patients with severe aplastic anemia who were unable to access or tolerate horse-ATG. They focused on evaluating a primary end point of the overall hematological response rate by 6 months in the intention-to-treat population. 

In this multicenter, single-arm, phase 2 study, 54 patients were included. All patients were given eltrombopag at 150 mg (excluding Asian patients [n = 22], who were instead given eltrombopag at 100 mg), and cyclosporin at 10 mg/kg per day (adjusted to a trough of 200 to 400 μg/L) from day 1 to 6 months. 

Study results demonstrated that 65% of patients (n = 35) completed 6 months of this regimen, and 11% (n = 6) completed the cyclosporin tapering period up to month 24. The overall hematological response rate by month 6 was 46% (n = 25). 

In terms of safety, the most commonly occurring adverse events reported were increased serum bilirubin (n = 22), nausea (n = 16), increased alanine aminotransferase concentration (n = 12), and diarrhea (n = 12). A total of 8 patients died while on this regimen, but no deaths were deemed related to the regimen. 

“Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia, with no unexpected safety concerns,” Scheinberg et al concluded. 

They added, “This approach might be beneficial where horse-ATG is not available or not tolerated.” 

Source:

Scheinberg P, Finelli C, Montaňo-Figueroa EH, et al. Activity and safety of eltrombopag in combination with cyclosporin A as first‑line treatment of adults with severe aplastic anaemia (SOAR): a phase 2, single-arm study. Lancet Haematol. Published online: February 6, 2024. doi: 10.1016/S2352-3026(23)00395-2