In patients with essential thrombocythemia (ET) who fail to respond to the initial therapy of hydroxyurea, the interferon drug ropeginterferon alfa-2b (ropeg) showed significantly improved responses and other important outcomes compared with the platelet-reducing agent anagrelide, new research suggests.

“Ropeg is now an approved option for patients with polycythemia vera (PV), and these [new] findings validate the role of ropeg in patients with the related condition of ET, in this case evidence for its benefit in the second-line setting,” senior author Ruben Mesa, MD, of the Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina, told Medscape Medical News.

Mesa was commenting on research that he and colleagues presented at Society of Hematologic Oncology (SOHO) 2025 held in Houston last week.

“If this leads to an additional FDA indication for ropeg in ET, it would be first approved new option for ET since anagrelide and would match the long-standing NCCN [National Comprehensive Cancer Network] guideline recommendations of considering a long-acting interferon for ET,” Mesa added.

For patients with high-risk ET, as many as a third are either intolerant of or fail to respond to the standard-of-care treatment of hydroxyurea. Anagrelide represents a standard second-line agent, however, no new therapy has been approved for ET in the US since anagrelide was approved in 1997.

ET, a myeloproliferative neoplasm, is a rare chronic blood cancer. Also known as primary thrombocythemia, this bone marrow disorder causes the overproduction of abnormal platelets.

Ropeg is currently approved for the treatment of PV, which, like ET, is also a Philadelphia chromosome-negative myeloproliferative neoplasm, hence raising the interest in its potential use for ET, however, the drug is not currently approved for ET.

To investigate, the researchers conducted the phase 3 SURPASS-ET randomized trial, enrolling 174 patients with ET who were intolerant or refractory to hydroxyurea.

Patients in the ropeg group (n = 91) were treated with a starting dose of 250 mcg, titrating to 350 mcg at week 2 and then, if tolerated, to 500 mcg from week 4 every 2 weeks.

The median age was 61 years in the ropeg group and 64 years in the anagrelide group; the groups were about half women; the median spleen size was somewhat smaller in the ropeg group (median, 13.10 cm vs 15.15) with no significant differences in other characteristics.

The study’s primary endpoint was response to modified European LeukemiaNet criteria, including at least a 10-point decrease in Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score for at least 12 weeks, normalization of peripheral blood counts for at least 12 weeks, absence of vascular events and disease progression, and disappearance of bone marrow histological abnormalities.

The primary endpoint was met at 9 and 12 months by 42.9% in the ropeg group vs just 6% in the anagrelide group (P = .0001).

Specifically, the platelet count response rate was met in 56% in the ropeg group vs 21.7% in the anagrelide group, white blood cell count response was achieved in 73.6% vs 13.3%, and peripheral blood count remission was achieved in 56% vs 6.0%.

In further outcomes, improvement or nonprogression of splenomegaly occurred in 87.9% and 54.2% of ropeg and anagrelide patients, respectively, and an absence of hemorrhagic or thrombotic events occurred in 84.6% and 51.8% of patients, respectively.

While no molecular response was observed in the anagrelide group, those in the ropeg group had 30.7% in JAK2 V617F and 30.0% in CALR molecular responses.

Grade 3 or higher adverse events occurred in 23.1% in the ropeg group vs 33.8% in the anagrelide group, and serious adverse events occurred in 15.4% vs 30.0%.

Adverse event-related discontinuations occurred in just 5.5% in the ropeg group vs 20.0% in the anagrelide group.

“Ropeg has very long-term follow-up for patients with PV, a disease with a very similar biology and natural history, so this is reassuring from a long-term safety and tolerability standpoint,” Mesa said.

Of note, ropeg is also discussed in the context of representing an important alternative to peginterferon alfa-2a (peg-IFN), which is also sometimes used for patients with ET who don’t respond to hydroxyurea, but which has faced global shortages due to increased use for myeloproliferative neoplasms and a change in manufacturer that significantly slowed supply.

In a letter published last spring in the Annals of Hematology, Mesa and colleagues highlighted ropeg as an important viable alternative to the “critical shortage of peg-IFN” and offered guidance on switching patients with ET as well as PV to ropeg.

“Our group has accumulated experience in transitioning patients from peg-IFN to ropeg-IFN due to historic insurance issues and clinical trial participation, allowing us to propose practical strategies for safe conversion,” they reported.

“A best-practice approach to dose equivalence, based on collective experience and real-world data, is pragmatic given that no formal head-to-head dosing trials exist.”

The dosing, as well as important monitoring recommendations, are detailed in their letter.

“It is logical, based on efficacy, safety, and impact of molecular burden of disease of ropeg for PV, that we would see similar benefits in trials with ET,” Mesa said. “SURPASS ET provides now phase 3 data proving the safety, efficacy, and impact on variant allele frequency for ET in the second line.”

This study was sponsored by PharmaEssentia. Mesa disclosed relationships with AbbVie, Blueprint, BMS, CTI, Genentech, Geron, GSK, Incyte, Morphosys, Novartis, Sierra, Sierra Oncology, and Telios.