Combo improves response rates in treatment-naïve SAA

Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.

Survival

The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.

Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.

Three patients died—1 while on study and 2 after transplant.

Clonal evolution and PNH

The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.

In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.

One patient with a complex karyotype progressed to acute myeloid leukemia.

Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).

Safety

Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.

Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.

AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.

The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry.