New data seem to confirm a class effect of TPO‐receptor agonists (TPO‐RA) in the setting of refractory aplastic anaemia.

Romiplostim appears to be effective in the same way as as eltrombopag in patients with aplastic anaemia refractory to immunosuppressive therapy, according to a preliminary study.

A phase 2/3 open-label trial conducted in Japan and Korea recruited 31 adult patients with aplastic anaemia and thrombocytopenia refractory to anti‐thymocyte globulin plus cyclosporine or cyclosporine monotherapy.

Patients received subcutaneous romiplostim at 10 µg/kg once weekly for 4 weeks followed by titrated dose steps of 5, 10, 15 and 20 µg/kg once weekly up to 52 weeks.

The romiplostim dose was adjusted depending on platelet response. The median dose (range) was 15·9 (3·1–18·8) µg/kg/week over the study for the 27 patients who completed at week 53.

The study, published in the British Journal of Haematology, found the primary end point – any of the defined haematological responses in platelets, erythrocytes or neutrophils at week 27 – was achieved in 84% of patients.

About 65% of patients had a defined platelet response, 74% for erythrocytes and 39% for neutrophils at 27 weeks, with similar results observed at 53 weeks.

The mean duration of haematological response was 251 days.

Of the patients who were transfusion dependent for both platelets and red blood cells, 83% were transfusion independent at 27 weeks, dropping to 75% at 53 weeks.

There were no significant differences between subgroups such as severe and non-severe aplastic anaemia, or based on previous therapy.

The most common treatment‐related AEs were headache (13%) and muscle spasms (13%). No patients discontinued romiplostim because of AEs.

The investigators said their 84% haematological response rate was higher than the expected rate of 40%, which was based on earlier study of eltrombopag in similar patients.

“The response rate in the present study was also higher than that of our previous romiplostim study, a French retrospective romiplostim study and the reference eltrombopag study, suggesting that a higher initial dose of romiplostim may be required for effective HSPC stimulation in patients with AA.”

They said that although romiplostim and eltrombopag act via a common mechanism of action as TPO mimetics, they do have different actions.

“Eltrombopag has been shown to stimulate haematopoiesis at the stem cell level through iron chelation‐mediated molecular re‐programming, whereas romiplostim does not exhibit iron‐chelating activity.”

“Furthermore, the agents have different locations for TPO‐receptor binding: romiplostim binds to the extracellular region of the receptor and eltrombopag to the transmembrane region.”

They added that the different mechanisms of action might explain why clonal evolution had been seen with eltrombopag but not been observed with romiplostim.

“In conclusion, the use of a higher starting dose of romiplostim followed by dose titration was effective and well tolerated in the treatment of patients with AA refractory to IST,” they said.

A Commentary, also published in BJHaem, said the findings could change practice if they were confirmed in larger studies or in real‐world experience.

“These data confirm the class effect of TPO‐RA in the setting of refractory AA and further ongoing studies with romiplostim and other novel TPO mimetics like avatrombopag will add therapeutic options in this rare disease.”

The study would require validation in non-Asian and paediatric populations, the Commentary said.