Eltrombopag with or without Tacrolimus for relapsed/refractory acquired aplastic anaemia: a prospective randomized...

Area of Science:

• Hematology
• Clinical Trials
• Pharmacology

Background:

• Acquired aplastic anemia (AA) is a rare, severe bone marrow failure disorder.
• Refractory/relapsed AA presents significant treatment challenges.
• Eltrombopag (EPAG) and tacrolimus are used in AA treatment, but combination efficacy requires further study.

Purpose of the Study:

• To compare the efficacy and safety of eltrombopag (EPAG) combined with tacrolimus versus EPAG monotherapy in patients with refractory/relapsed acquired aplastic anemia (AA).
• To evaluate overall response rate (ORR), survival, safety, and clonal evolution.
• To identify potential subgroups benefiting from combination therapy.

Main Methods:

• A randomized trial comparing EPAG+tacrolimus (n=76) to EPAG monotherapy (n=38) in refractory/relapsed AA patients.
• Median follow-up of 18 months.
• Assessment of ORR at 3, 6, 12 months, and last follow-up; safety, overall survival, and clonal evolution were also monitored.

Main Results:

• While ORR at 3 months was similar (38.2% vs. 31.6%), EPAG+tacrolimus showed significantly higher ORR at 6 months (61.8% vs. 39.5%, P=0.024) and last follow-up (60.5% vs. 34.2%, P=0.008).
• No significant differences in adverse events, overall survival (P=0.635), or clonal evolution (P=1.000) were observed.
• Subgroup analysis indicated EPAG+tacrolimus improved ORR at 6 months and last follow-up, and cumulative relapse-free survival in patients <60 years old.

Conclusions:

• Combination therapy with eltrombopag and tacrolimus demonstrates superior response rates in refractory/relapsed acquired aplastic anemia compared to eltrombopag monotherapy.
• The combination therapy appears safe and does not negatively impact survival or clonal evolution.
• Younger patients (<60 years) may particularly benefit from the addition of tacrolimus to eltrombopag treatment.