The SURPASS-ET study was studying second-line therapy for patients with essential thrombocythaemia. Essential thrombocythaemia is a chronic myeloproliferative neoplasm characterised by molecular mutations JAK2 and CALR, sometimes MPL. Patients have thrombocytosis, they can have leucocytosis, risk of thrombosis and bleeding.

Currently our treatment options are quite limited and include hydroxyurea, which has been historical therapy but with limitations, and then anagrelide, approved both in Europe and in the States but with toxicity and not the ideal second-line therapy.

The trial was to investigate in a randomised way long-acting interferon, ropeginterferon alfa-2b, versus anagrelide in the second-line setting for those that had failed hydroxyurea. Ropeginterferon is also approved in the cousin and related disease of polycythemia vera.

What was the methodology and what were the findings?

The study was a randomised phase III trial between pegylated interferon, or ropeginterferon alfa-2b, in a 1:1 randomisation with anagrelide, with a dosing schedule for each of those medications, with a primary endpoint of improvement in modified ELN response, which was control of counts, a lack of progression or response in spleen and symptoms and a lack of thrombo events or haemorrhagic events, with endpoints being measured at both 9 and 12 months.

What are the clinical implications of these findings?

The key findings for the study were, one, for the primary endpoint – modified ELN response – ropeginterferon was clearly superior to anagrelide – 43% to 6%. In each subcomponent of that, improvement in the platelets, the white cell count, spleen symptoms and lack of events, was statistically significant, favouring the ropeginterferon arm.

Secondary endpoints in terms of improvement in molecular findings was clearly statistically significant for those with the JAK2 mutation, with a clear decrease for patients with the JAK2 on ropeginterferon and an increase for those with anagrelide. The number of patients with the [??] mutation was smaller, so it didn’t reach statistical significance but clearly there was a clear difference in the data with a reduction in CALR-related variant allele frequency and increase for those on the anagrelide arm.

Finally, in terms of safety it strongly favoured ropeginterferon. One, greater number of adverse events on the anagrelide arm, particularly more serious treatment-emergent adverse events. Two, there were eight thromboembolic events on the anagrelide arm to one on the ropeginterferon arm. Additionally, there were three deaths on the anagrelide arm, for a range of reasons but myocardial infarction, pneumonia, COVID-related pneumonia, and none on the ropeginterferon arm.

So our takeaway is that ropeginterferon was clearly superior to anagrelide as second-line therapy on the basis of efficacy, primary and secondary endpoints, and on the basis of safety.

Is there anything else you would like to add?

Ropeginterferon has clearly made a strong impact in polycythemia vera and we feel that these data really support the broader use and registration of ropeginterferon alfa-2b now for essential thrombocythemia.