Imatinib dose reduction in major molecular response of chronic myeloid leukemia: Results from the German chronic myeloid leukemia-study IV

Christian Michel, Andreas Burchert, Andreas Hochhaus, Susanne Saussele, Andreas Neubauer, Michael Lauseker, Stefan W. Krause, Hans Jochem Kolb, Dieter Kurt Hossfeld, Christoph Nerl, Gabriela M. Baerlocher, Dominik Heim, Tim H. Brümmendorf, Alice Fabarius, Claudia Haferlach, Brigitte Schlegelberger, Leopold Balleisen, Maria Elisabeth Goebeler, Mathias Hänel, Anthony HoJolanta Dengler, Christiane Falge, Robert Möhle, Stephan Kremers, Michael Kneba, Frank Stegelmann, Claus Henning Köhne, Hans Walter Lindemann, Cornelius F. Waller, Karsten Spiekermann, Wolfgang E. Berdel, Lothar Müller, Matthias Edinger, Jiri Mayer, Dietrich W. Beelen, Martin Bentz, Hartmut Link, Bernd Hertenstein, Roland Fuchs, Martin Wernli, Frank Schlegel, Rudolf Schlag, Maike de Wit, Lorenz Trümper, Holger Hebart, Markus Hahn, Jörg Thomalla, Christof Scheid, Philippe Schafhausen, Walter Verbeek, Michael J. Eckart, Winfried Gassmann, Michael Schenk, Peter Brossart, Thomas Wündisch, Thomas Geer, Stephan Bildat, Erhardt Schäfer, Joerg Hasford, Rüdiger Hehlmann, Markus Pfirrmann

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg (‘high-dose’) imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients. Study protocol registered at clinicaltrials.gov 00055874.

Original languageEnglish
Pages (from-to)955-962
Number of pages8
JournalHaematologica
Volume104
Issue number5
DOIs
StatePublished - 30 Apr 2019
Externally publishedYes

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