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4539 ELN Treatment Milestones in Chronic Myeloid Leukemia Are Prognostic for Achieving Deep Molecular Response and Treatment-Free Remission in Routine Care: Results of the German CML Registry

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, adult, Clinical Research, CML, Chronic Myeloid Malignancies, Diseases, real-world evidence, registries, Myeloid Malignancies, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Katharina Kohlbrenner1*, Norbert Galuschek1*, Alice Fabarius1*, Marcel Reiser2*, Klaus Fenchel3*, Eva Esseling, MD4*, Thomas Göhler5*, Ralf-Bodo Kühn6*, Reinhard Depenbusch7*, Ivo Talah Azeh8*, Erik Engel9*, Richard Hansen10*, Mathias Hanel, MD11, Paul Jehner12*, Maisun Abu-Samra13*, Markus Ritter14*, Norbert Gattermann, MD15, Henning Pelz16*, Stefan Fuxius17*, Burkhard Oswald18*, Gabriela M Baerlocher, MD19,20*, Tim H. Brümmendorf21,22, Dominik Heim23*, Philipp le Coutre, MD24*, Andreas Burchert, MD25, Dietger Niederwieser, MD, PhD26*, Hans Tesch, MD27*, Wolf-Karsten Hofmann, MD1*, Andreas Hochhaus, MD28, Rüdiger Hehlmann, MD 29,30 and Susanne Saussele, MD 1

1Medizinische Fakultät Mannheim, III. Medizinische Universitätsklinik, Universität Heidelberg, Mannheim, Germany
2Praxis für internistische Onkologie und Hämatologie (PIOH), Frechen, Germany
3Schwerpunktpraxis für Onkologie und Hämostaseologie, MVZ Saaletal, Saalfeld, Germany
4Medizinische Klinik A, Universitätsklinikum Münster, Münster, Germany
5Onkozentrum Dresden/Freiberg/Meißen, Dresden, Germany
6Onkologische Praxis Oldenburg/Delmenhorst, Oldenburg, Germany
7Onkologische Gemeinschaftspraxis Dres. Depenbusch, Schütt und Sonnenberg, Gütersloh, Germany
8Onkologische Gemeinschaftspraxis und Tagesklinik Dres. Schardt & Azeh, Gelsenkirchen, Germany
9Hämatologisch-Onkologische Praxis Altona (HOPA), Hamburg, Germany
10Onkologische Gemeinschaftspraxis Dres . Hansen und Reeb, Kaiserslautern, Germany
11Department of Internal Medicine III, Klinikum Chemnitz, Chemnitz, Germany
12Onkologische Praxis Moers, Moers, Germany
13Medizinische Klinik IV und Poliklinik für Hämatologie, Universitätsklinikum Gießen und Marburg, Campus Gießen, Gießen, Germany
14Klinik für Innere Medizin - Hämatologie / Onkologie, Klinikum Sindelfingen-Böblingen, Sindelfingen, Germany
15Klinik für Hämatologie, Onkologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
16Onkologie Offenburg, Offenburg, Germany
17Onkologische Schwerpunktpraxis Heidelberg, Heidelberg, Germany
18Onkologische Schwerpunktpraxis Worms, Worms, Germany
19Universitätsklinik für Hämatologie, Inselspital Bern, Bern, Switzerland
20Department for BioMedical Research (DBMR), Laboratory for Hematopoiesis and Molecular Genetics, Universität Bern, Bern, Switzerland
21Medizinische Klinik IV, Universitätsklinikum RWTH Aachen, Aachen, Germany
22Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany
23Klinik für Hämatologie, Universitätsspital Basel, Basel, Germany
24Charité-Universitätsmedizin Berlin, Berlin, Germany
25Hämatologie, Onkologie und Immunologie, Universitätsklinikum Gießen und Marburg, Standort Marburg, Marburg,, Germany
26Abteilung Hämatologie und lnternistische Onkologie, Universitätsklinikum Leipzig, Lepzig, Germany
27Centrum für Hämatologie und Onkologie Bethanien, Frankfurt am Main, Germany
28Klinik für Innere Medizin II, Abt. Hämatologie und lnternistische Onkologie, Universitätsklinikum Jena, Jena, Germany
29Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany
30ELN Foundation, Weinheim, Germany

Introduction: Tyrosine kinase inhibitor (TKI) induced molecular response (MR) within the first months after diagnosis of chronic myeloid leukemia (CML) is critical for long-term outcome prediction.

Aim: To analyze the prognostic relevance of MR according to European Leukemia Net (ELN) treatment milestones in CML patients in routine care.

Methods: Within the German CML registry, adult patients (pts) with CML newly diagnosed between 2013 and 2019 were registered and followed annually. Endpoints included time to MR, progression and death. MR was analyzed according to the ELN recommendations 2013 with the focus on the BCR::ABL1 (International Scale, IS) milestones 10% (EMR, early molecular response) at 3 months (M3), 1% (MR2) at 6 months (M6) and 0.1% (MMR, major molecular response) at 12 months (M12) using the cumulative incidence function. MR at milestones were correlated to achievement of DMR (deep molecular remission, defined as BCR::ABL1IS < 0.01%).

Results: A total of 540 pts have been registered from 91 centers. Thirty pts had to be excluded (inclusion failure), 510 pts were evaluable for baseline analyses and 490 pts for MR analyses. Median age at diagnosis was 59 years (range 16-100), 264 pts of 510 pts (52%) were male. Median follow-up was 5.4 years. First-line treatment included imatinib ([n=209 (42%)], nilotinib [n=141 (29%)], dasatinib [n=146 (29%)], HU only (n=2 (0,4%)], and was unknown for 12 pts. In total, 473 (97%) of 490 pts achieved an EMR after a median of 3 months (mth) [range (r) 0-55 mth], 461 (94%) pts MR2 [median 5 mth (1-67 mth)], and 446 (91%) pts MMR [median of 9 mth (1-82 mth)]. DMR was achieved in a total of 384 (78%) pts after a median of 15 mth (1-96 mth) of which at least 282 (58%) had a MR level according to MR4.5 (BCR::ABL1 <0.0032%). Milestones M3, M6, and M12 were achieved in 245 (50%), 292 (60%), and 297 (61%) pts, respectively (see Table). DMR was achieved in 208 (85%), 259 (89%) and 277 (93%) pts who reached M3, M6, and M12, respectively. In all other pts only 176 (72%), 125 (63%), and 107 (55%) pts achieved DMR.

61 (12%) pts stopped TKI-treatment with the aim of treatment-free remission (TFR). Of these pts, 40 (66%), 47 (77%), and 52 (85%) pts achieved M3, M6, and M12 before TKI stop, respectively. 26 (43%) pts lost MMR in TFR.

Progression to either accelerated phase (AP) or blast phase (BP) was documented for 9 patients (6 BP, 3 AP). Progression was more frequent in pts without achievement of milestones. At M3 2.4% vs. 1.2%, M6 3.5% vs. 0.7% and M12 4.7% vs. 0% of pts progressed. 48 deaths were reported. Only one death was clearly CML-related. This pt reached M3 but not M6 and M12, and died in BP.

7 pts developed BCR::ABL1 mutations. According to milestones, mutations were found in 1.2%, 1%, and 1% with achievement of M3, M6 and M12 vs. 1.6%, 1.5%, and 1.6% of pts not achieving the respective milestones. In addition, 126 pts (29%) lost MMR without being in TFR regardless of whether the milestones had been reached or not. Reasons for MMR-loss were variable (dose-reduction because of intolerance, incompliance, age) so that no correlation to treatment milestones can be made.

Conclusion: Achieving ELN milestones in CML in routine care demonstrated a better outcome for pts with higher DMR rates, lower rates for progression rates and kinase domain mutations. DMR is of importance for stopping treatment in CML. Consequently, the rate of pts who could start TFR after achieving the ELN-milestones was 2-3 times higher than of pts who failed milestones or with unknown MR results.

Disclosures: Hanel: Novartis: Research Funding. Ritter: Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria. Gattermann: BMS: Honoraria; Novartis: Honoraria; Takeda: Research Funding. Pelz: Roche Pharma AG: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Baerlocher: Novartis: Research Funding; MSD: Research Funding; Geron Corporation: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Brümmendorf: Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Speakers Bureau. le Coutre: Incyte: Honoraria; Blueprint: Honoraria; AOP: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria. Burchert: Novartis: Honoraria, Research Funding; MSD: Research Funding; Incyte: Honoraria. Hochhaus: Bristol Myers Squibb: Consultancy, Research Funding; Incyte: Research Funding; Pfizer: Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Saussele: Incyte: Research Funding; BMS: Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Roche: Consultancy.

*signifies non-member of ASH