Eltrombopag for Bone Marrow Failure in Fanconi Anemia: Results From the Phase II Clinical Trial FANCREV

Eltrombopag stimulates hematopoiesis in aplastic anemia, and preclinical studies suggest it promotes DNA repair in Fanconi Anemia (FA) hematopoietic stem cells. We conducted a clinical trial to explore its safety and efficacy in bone marrow failure due to FA. Eltrombopag was administered to 8 pediatric patients with one or more significant cytopenias. After 6 months, those who achieved at least a partial response in peripheral blood continued treatment for 6 additional months. Median age was 7 years (4-12), one patient had somatic mosaicism in bone marrow, and two had been treated by gene therapy (GT). At 6 months, three patients (37.5%) achieved a response, persisting in one at 12 months. The three patients with either somatic mosaicism or with GT-corrected cells showed an enhanced increase of corrected cells. One patient required dose modifications due to gastrointestinal intolerance and two because of hepatobiliary laboratory toxicity. No clonal evolution was observed by conventional cytogenetics, but a patient developed a transient somatic variant in RUNX1. In conclusion, eltrombopag did not mediate clinically relevant responses, although a possible impact of dose reductions and treatment duration must be considered. The increase of gene-corrected cells suggests it promoted a proliferative advantage over uncorrected ones. Www.clinicaltrials.gov #NCT06045052.