Randomized phase 3 trial of Ropeginterferon alfa-2b versus surveillance after tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia (ENDURE/CML-IX).

Burchert A, Nicolini FE, le Coutre P, Saussele S, Hochhaus A, Tuere E, Metzelder SK, Pauck K, Garn H, Raifer H, Huber M, Gattermann N, Crysandt M, Schafhausen P, Bormann M, Radsak MP, Guerci-Bresler A, Illmer T, Goebeler ME, Herhaus P, Teichmann LL, Franke GN, Lang F, Krause S, Möhle R, Klausmann M, Stegelmann F, Lutz C, Etienne G, Stoltefuß A, Göthert JR, Ernst T, Abu-Samra M, Höffkes HG, Neubauer A, Wang Y, Weiland P, Otto C, Kiessler L, Weber T, Kroning L, Nist A, Stiewe T, Hehlmann R, Aminossadati B, Wittenberg M, Winterstein K, Oellerich T, Lechner M, Pfirrmann M, Schade-Brittinger C, Klemm P, Michel C (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 40

Pages Range: 410-417

Journal Issue: 2

DOI: 10.1038/s41375-025-02859-1

Abstract

Treatment-free remission (TFR) after discontinuation of ABL tyrosine kinase inhibitors (TKIs) is an important therapeutic goal in chronic myeloid leukemia (CML). Interferon-α (IFN) has been suggested to promote durable TFR. The phase 3 ENDURE trial (NCT03117816; EUDRA-CT 2016-001030-94) prospectively tested this hypothesis in patients with stable deep molecular remission after TKI therapy. A total of 203 patients were randomised 1:1 to receive ropeginterferon alfa-2b (ropeg-IFN; 100 µg subcutaneously every two weeks for 15 months, n = 95) or observation alone (n = 108) after TKI discontinuation. The primary endpoint was molecular relapse-free survival (MRFS), defined as time to loss of major molecular response (MMR) or death. At a median follow-up of 36 months, 25-month MRFS was 56% (95% confidence interval (CI), 45-66) with ropeg-IFN and 59% (95% CI, 49-68) with observation (hazard ratio (HR), 1.02; 95% CI, 0.68-1.55; P = 0.91). Among 83 patients with molecular data after TKI restart, 79 (95%) regained at least MMR, 78 within 12 months (median 3 months, interquartile range: 2-4 months). Ropeg-IFN was well tolerated (median administered dose of 92 µg, range 3-104), and no new safety signals were observed. Ropeg-IFN maintenance did not improve the probability of sustained TFR after TKI discontinuation.

Authors with CRIS profile

Involved external institutions

Ruprecht-Karls-Universität Heidelberg Germany (DE) Universitätsklinikum Jena Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Philipps-Universität Marburg Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Universitätsklinikum Aachen (UKA) Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Klinikverbund Bremen (Gesundheit Nord) Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Praxis für Hämatologie und Onkologie Koblenz Germany (DE) Onkozentrum Dresden/Freiberg Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE) Centre Hospitalier Lyon Sud (CHLS) France (FR) Charité - Universitätsmedizin Berlin Germany (DE) Klinikum rechts der Isar Germany (DE) Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf (CIO ABCD) Germany (DE) Universität Leipzig Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Eberhard Karls Universität Tübingen Germany (DE) Universitätsklinikum Ulm Germany (DE) Institut Bergonié France (FR) Evangelisches Krankenhaus Hamm Germany (DE) Universitätsklinikum Essen Germany (DE) Klinikum Fulda Germany (DE) Hôpital Brabois Adultes France (FR) Ludwig-Maximilians-Universität (LMU) Germany (DE)

How to cite

APA:

Burchert, A., Nicolini, F.E., le Coutre, P., Saussele, S., Hochhaus, A., Tuere, E.,... Michel, C. (2026). Randomized phase 3 trial of Ropeginterferon alfa-2b versus surveillance after tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia (ENDURE/CML-IX). Leukemia, 40(2), 410-417. https://doi.org/10.1038/s41375-025-02859-1

MLA:

Burchert, Andreas, 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 40.2 (2026): 410-417.

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