A Burchert, Franck E. Nicolini, P. le Coutre, Susanne Saußele, Andreas Hochhaus, Evin Tuere, Stephan K. Metzelder, Kim Pauck, Holger Garn, Hartmann Raifer, Magdalena Huber, Norbert Gattermann, Martina Crysandt, Philippe Schafhausen, Matthias Bormann, Markus P. Radsak, Agnès Guerci‐Bresler, Thomas Illmer, Maria Elisabeth Goebeler, Peter Herhaus, Lino L. Teichmann, Georg-Nikolaus Franke, Fabian Lang, Stefan W. Krause, Robert Möhle, Martine Klausmann, Frank Stegelmann, Christoph Lutz, G. Etienne, Andrea Stoltefuß, J Göthert, Thomas Ernst, Maisun Abu-Samra, Heinz‐Gert Höffkes, A Neubauer, Ying Wang, Paul Weiland, Clara Otto, Lea Kiessler, Theresa Weber, Lea Kroning, Andrea Nist, Thorsten Stiewe, R. Hehlmann, Behnaz Aminossadati, Michael Wittenberg, Kerstin Winterstein, Thomas Oellerich, Marcus Lechner, Markus Pfirrmann, Carmen Schade-Brittinger, Paul Klemm, Christian Michel
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.