ENDURE: No Added Benefit With Ropeginterferon Alfa-2b After TKI Stoppage in CML

Results from the phase 3 ENDURE trial (NCT03117816), newly published in Leukemia, demonstrate that ropeginterferon alfa-2b maintenance therapy confers no additional benefit over observation alone after tyrosine kinase inhibitor (TKI) cessation in patients with chronic myeloid leukemia (CML).¹

At a median follow-up of 36 months, the molecular relapse-free survival (MRFS) at 25 months with ropeginterferon alfa-2b and observation was 56% (95% CI, 45%–66%) and 59% (95% CI, 49%–68%), respectively (HR, 1.02; 95% CI, 0.68–1.55; P =.91), suggesting no clinically meaningful improvement in probability of treatment-free remission after TKI discontinuation despite previous biological hypotheses.

A total of 90 patients had lost major molecular remission (MMR) after TKI cessation. However, among 83 patients with available molecular data after restarting TKI, a large majority (95%) had regained MMR within 12 months (median, 3 months). These high rates of regained MMR after TKI restart highlight the reversibility of molecular relapse and the importance of close molecular monitoring.

“Although the ENDURE trial failed to confirm a benefit in its primary end point, it was crucial in objectively testing and contextualizing previous nonrandomized or translational evidence that had suggested an interferon-related improvement in [treatment-free remission (TFR)] rates,” wrote study authors Burchert et al.¹ “In this sense, the ENDURE trial may be regarded as concluding the long-standing exploration of [interferon-α; IFN]-based strategies in CML, pending a clearer mechanistic distinction between IFN- and TKI-associated pathways to TFR.”

Safety Profile

The median administered dose in the ropeginterferon arm was 92 µg over the planned 15-month maintenance period. Ropeginterferon alfa-2b was generally well tolerated, with no new or unexpected safety signals observed.

Of the safety population (n = 202), 86.1% experienced at least 1 adverse event (AE), which were generally consistent with known interferon toxicity profiles. AEs were primarily low-grade, regardless of arm. Importantly, there were no CML-specific deaths. In light of these data, the authors remarked that the toxicity profile of ropeginterferon alfa-2b was favorable compared with other IFN formulations.

ENDURE Study Design

The ENDURE trial was a randomized, multicenter, open-label study designed to evaluate the efficacy and safety of ropeginterferon alfa-2b in patients with CML who discontinue TKI therapy.² The primary end point of the study was MRFS, defined as loss of MMR.

Enrolling adult patients across centers in France and Germany between May 2017 and June 2021, the study included those with BCR::ABL1-positive chronic phase CML who were on TKI monotherapy treatment for a minimum for 3 years and were in deep molecular remission for at least 1 year.

A total of 203 patients were randomized 1:1 to receive either ropeginterferon alfa-2b maintenance therapy (n = 95) or surveillance only, with no further treatment after TKI discontinuation (n = 108). Those assigned to the treatment arm received ropeginterferon alfa-2b at 50 µg subcutaneously every 2 weeks followed by 100 µg every 2 weeks thereafter up to month 15.

REFERENCES

1. Burchert A, Nicolini FE, le Coutre P, et al. Randomized phase 3 trial of Ropeginterferon alfa-2b versus surveillance after tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia (ENDURE/CML-IX). Leukemia. Published online January 12, 2026. doi:10.1038/s41375-025-02859-1

2. ENDURE - Efficacy and safety of AOP2014 with CML patients in remission (ENDURE-CML-IX). ClinicalTrials.gov. Updated March 31, 2023. Accessed January 14, 2026. https://clinicaltrials.gov/study/NCT03117816