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Chronic lymphocytic leukemia

Prognostic model for newly diagnosed CLL patients in Binet stage A: results of the multicenter, prospective CLL1 trial of the German CLL study group

Leukemia volume 34, pages 1038–1051 (2020)Cite this article

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Abstract

The heterogeneity of early stage CLL challenges prognostication, and refinement of prognostic indices for risk-adapted management in this population is essential. The aim of the multicenter, prospective CLL1 trial was to explore a novel prognostic model (CLL1-PM) developed to identify risk groups, separating patients with favorable from others with dismal prognosis. A cohort of 539 clinically, biochemically, and genetically characterized Binet stage A patients were observed until progression, first-line treatment, or death. Multivariate analysis identified six independent factors associated with overall survival (OS) and time-to-first treatment (TTFT): del(17p), unmutated IGHV, del(11q), ß2-microglobulin >3.5 mg/dL, lymphocyte doubling time (LDT) <12 months, and age >60 years. These factors were integrated into the CLL1-PM, which stratified patients into four risk groups. The CLL1-PM was prognostic for OS and TTFT, e.g., the risk of treatment at 5 years was 85.9, 51.8, 27.6, and 11.3% for very low (0–1.5), low (2–4), high (4.5–6.5), and very high-risk (7–14) scores, respectively (P < 0.001). Notably, in addition to factors comprising CLL-IPI, we substantiated del(11q) and LDT as prognostic factors in early CLL. Altogether, our findings would be useful to effectively stratify Binet stage A patients, particularly within the scope of clinical trials evaluating novel agents.

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Fig. 1: Overall survival according to the CLL1-PM risk groups.
Fig. 2: Time-to-first-treatment according to the CLL1-PM risk groups.
Fig. 3: Overall survival of the CLL1 cohort according to the CLL-IPI risk groups.
Fig. 4: Time to first treatment of the CLL1 cohort according to CLL-IPI risk groups.

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Acknowledgements

The authors would like to thank Anne Westermann, Ute Elberskirch, Anna Fink, MD, Can Zhang, PhD, Thu-Trang Pham, PhD, Emily Koeneke, PharmD, and Katrin Klein for their contribution to this work. The trial was supported by grants from Deutsche Krebshilfe (German Cancer Aid) (70–2434 and 106116), Wilhelm-Sander-Foundation (2001.004.1 and 2001.004.2), and BayerSchering Pharma AG. Study drug was provided by BayerSchering Pharma AG, which did not have a role in the design or conduct of the study, writing of the manuscript, or the decision to submit the manuscript for publication. Data collection was supported by the Kompetenznetz Maligne Lymphome e.V. (Secretary: Birgit Fath, PhD).

Funding

The trial was funded by Deutsche Krebshilfe (German Cancer Aid) (70–2434 and 106116), Wilhelm-Sander-Foundation (2001.004.1 and 2001.004.2), and BayerSchering Pharma AG.

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Author notes

  1. These authors contributed equally: Hartmut Döhner, Stephan Stilgenbauer, Michael Hallek

Authors and Affiliations

  1. Department of Internal Medicine I, München Klinik Schwabing, Munich, Germany

    Manuela A. Hoechstetter, Clemens Wendtner & Michael Starck

  2. Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany

    Raymonde Busch

  3. Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany

    Barbara Eichhorst, Jasmin Bahlo, Sandra Robrecht, Clemens Wendtner, Kirsten Fischer, Carmen D. Herling & Michael Hallek

  4. Department of Internal Medicine II, Klinikum Ingolstadt, Ingolstadt, Germany

    Andreas Bühler & Dirk Winkler

  5. Internal Medicine, Hematology and Oncology Private Practice, Erlangen, Germany

    Michael J. Eckart

  6. Oncological Private Practice, Landshut, Germany

    Ursula Vehling-Kaiser

  7. Internal Medicine, Hematology and Oncology Private Practice, Saarbrücken, Germany

    Georg Jacobs

  8. Department of Internal Medicine I, Division of Hematology and Hemostaseology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Ulrich Jäger

  9. Internal Medicine, Hematology and Oncology Private Practice, Halle, Germany

    Hans Jürgen Hurtz

  10. Department of Internal Medicine I, Division of Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria

    Georg Hopfinger

  11. Department of Hematology and Oncology, Klinikum Lippe-Lemgo, Lemgo, Germany

    Frank Hartmann

  12. Department of Hematology, Oncology and Palliative Medicine, Klinikum Bad Saarow, Bad Saarow, Germany

    Harald Fuss

  13. Hematology and Oncology Private Practice, Munich, Germany

    Wolfgang Abenhardt

  14. Hematology and Oncology Private Practice, Berlin, Germany

    Ilona Blau

  15. Hematology and Oncology Private Practice, Hildesheim, Germany

    Werner Freier

  16. Hematology and Oncology Private Practice, Leer, Germany

    Lothar Müller

  17. Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany

    Maria Goebeler

  18. Department of Internal Medicine III, Klinikum Karlsruhe, Karlsruhe, Germany

    Martin Bentz

  19. Interdisciplinary Oncology Center (IOZ) Private Practice, Munich, Germany

    Bertold Emmerich

  20. Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany

    Hartmut Döhner & Stephan Stilgenbauer

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  1. Manuela A. Hoechstetter
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Correspondence to Michael Hallek.

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Hoechstetter, M.A., Busch, R., Eichhorst, B. et al. Prognostic model for newly diagnosed CLL patients in Binet stage A: results of the multicenter, prospective CLL1 trial of the German CLL study group. Leukemia 34, 1038–1051 (2020). https://doi.org/10.1038/s41375-020-0727-y

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