Eltrombopag newly features in new guidelines for the diagnosis and management of aplastic anaemia (AA), with experts backing its use in the as yet unlicensed first-line setting.

In updated guidance published in the British Journal of Haematology, use of the thrombopoietin (TPO) receptor agonist has been endorsed as standard first-line treatment alongside anti-thymocyte globulin (ATG)-based immunosuppressive therapy for newly diagnosed acquired severe or very severe AA.

However, the drug should only be considered in the absence of a matched sibling donor for allogeneic haematopoietic stem cell transplantation (HSCT), and should be used “with meticulous long-term monitoring for clonal evolution”, the UK-based guideline group noted.

The guideline authors recommended earlier use of eltrombopagin the treatment pathway – pending regulatory approval – on the back of a Phase III study that compared first-line ATG and ciclosporin with or without eltrombopag for severe or very severe AA.

This showed that the drug induced a significant increase in complete response (CR) compared with standard immunosuppressive therapy at both 3 (22% vs 10%) and 6 months (68% vs 41%), with a shorter median time to response (3 vs 8.8 months) and without a compromise in treatment tolerability.

While there didn’t seem to be a difference on two-year overall survival between the two treatment arms, longer-term data will be necessary to determine ciclosporin and eltrombopag dependence, late relapses and clonal evolution, the group noted. 

Guideline author Dr Austin Kulasekararaj, Consultant Haematologist at King’s College Hospital, London, told the limbic that other key changes for clinical practice within the updated guidelines relate to investigations to ascertain the cause of disease, and the movement of age boundaries for HSCT in patients with severe acquired AA by one decade.

Up-front HSCT from a MSD is currently indicated for young and adult patients aged under 40 years. The guideline authors highlighted data demonstrating that similar outcomes can be achieved in older patients aged 40-50 years, but also emphasised that “comorbidities should be carefully assessed to determine fitness for up-front transplantation instead of immunosuppressive therapy” in this older subset. 

Dr Kulasekararaj stressed that haematologists should familiarise themselves with the updated guidelines to ensure that they can quickly detect and treat the disease, which is still very rare, but can be life-threatening.

“Patients can present acutely at hospital needing blood platelets and with infection complications, and while they are sometimes treated at referrals centres diagnostic workup is mostly done by general haematologists,” he noted.