Ruben A. Mesa, MD, on Essential Thrombocythemia: SURPASS-ET Trial

I'm so excited to be presenting on behalf of my colleagues and I the SURPASS ET study. The SURPASS ET study is a phase 3 trial for patients with essential thrombocythemia. This myeloproliferative neoplasm has goals of therapy of control of the blood counts to decrease risk of blood clots and bleeding and ideally try to control disease-associated symptoms and avoid progression in the disease. Currently there are relatively few available options for patients with ET: hydroxyurea, a long-standing therapy that is cytoreductive, and anagrelide, an approved therapy that is selective for reducing only platelets. The trial was ropegylated interferon alpha 2b versus anagrelide in the second-line setting. So patients with ET, high risk, symptomatic, needing therapy, who have failed hydroxyurea—either resistant or intolerant. Ropegylated interferon alpha 2b is a long-acting interferon approved in polycythemia vera, a cousin disease of essential thrombocythemia. It was a 1:1 randomization between anagrelide and ropegylated interferon alpha 2b, and we identified and described at this year's ASCO meeting that Ropeg was vastly superior to anagrelide in each way that we looked at it. First, in meeting the primary endpoint, which was the modified European LeukemiaNet criteria, which was control of the blood counts—the platelets and the white blood cells—improvement in symptoms, no vascular events. Second, as we looked at secondary endpoints, the individual components of response, each of those was superior for Ropeg versus anagrelide: control of counts, control in symptoms, lack of progression or improvement in splenomegaly, lack of progression or improvement in symptoms. Additionally, we had secondary endpoints related to molecular markers—the JAK2 V617F and CALR mutations—which were present in the vast majority of patients who were registered. Regarding JAK2, there was a statistically superior decrease in the JAK2 allele burden for those on Ropeg versus anagrelide, and then for CALR, it was a smaller number of patients. There was a clear difference between the two arms favoring Ropeg, although the numbers were too small to reach statistical significance. In terms of toxicity, that too favored ropegylated interferon. There were low-grade toxicities in both arms, but there were higher numbers of significant adverse events in the anagrelide arm, and there were three deaths in the anagrelide arm and zero in the Ropeg arm. Additionally, vascular events favored the Ropeg arm—only one event in that group and eight events in the anagrelide group. So overall, this represents strong data supporting the use of ropegylated interferon alpha 2b as second-line therapy for patients with ET who have failed hydroxyurea based on safety, efficacy, as well as potential for disease modification based on the improvement in the mutation burden.