Essential thrombocythemia (ET) is associated with numerous difficult to manage symptoms, as well as increased risk of thrombosis and hemorrhage. Low-dose aspirin with hydroxyurea is used as the standard of care frontline treatment strategy in high-risk patients, but for the many who become hydroxyurea resistant or intolerant, limited options are available. Ruben Mesa, MD, UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX, discusses the design and aims of the upcoming Phase III randomized, active-controlled SURPASS-ET trial (NCT04285086) of ropeginterferon alfa-2b as second line therapy for patients with ET who have shown resistance or intolerance to hydroxyurea. Ropeginterferon will be investigated for safety, tolerability, and efficacy in a cohort of 130 patients randomized to ropeginterferon or anagrelide as second line therapy. More than 60 sites across the US and Asia are involved in the study and randomization has begun. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.