Phase II study of the triple combination of rabbit ATG, ciclosporin and eltrombopag in patients with transfusion-dependent aplastic anaemia: West Japan Hematology Study Group (W-JHS) AA02 trial.

The efficacy of a triple combination of rabbit anti-human thymocyte immunoglobulin (rATG), ciclosporin and eltrombopag (EPAG) was prospectively evaluated in patients with severe or transfusion-dependent non-severe aplastic anaemia (SAA) across 29 institutions in Japan. Sixty patients were enrolled, of whom 48 had SAA. The primary end-point, the haematological overall response rate at 12 weeks, was 52.6% (95% confidence interval, 39.0%-66.0%), increasing to 67.9% at 26 weeks. The most frequent grade 3/4 adverse event was febrile neutropenia (20.0%). One elderly patient with severe neutropenia died of sepsis. Progression to myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) was observed in one patient each. There was no association between the haematological response and high thrombopoietin levels, presence of paroxysmal nocturnal haemoglobinuria-type cells or Human Leukocyte Antigen (HLA) class I allele-lacking cells. Five patients (8.5%) had chromosomal abnormalities at baseline with no subsequent progression to MDS or AML. By 26 weeks, chromosomal abnormalities had emerged or expanded in eight patients (17.4%), although abnormalities of chromosome 7 were not observed within 52 weeks. These results suggest that triple therapy with rATG may be as effective as that with horse anti-human thymocyte immunoglobulin. Notably, the addition of EPAG did not induce chromosomal abnormalities associated with poor prognosis.