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Chronic lymphocytic leukemia

Residual abdominal lymphadenopathy after intensive frontline chemoimmunotherapy is associated with inferior outcome independently of minimal residual disease status in chronic lymphocytic leukemia

Leukemia volume 34, pages 924–928 (2020)Cite this article

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In chronic lymphocytic leukemia (CLL), chemoimmunotherapies (CIT) and combinations with novel agents have proven to be highly effective with regard to eradication of minimal residual disease (MRD), while complete remissions (CR) are frequently not achieved due to residual lymphadenopathy [1, 2]. We have previously reported that undetectable MRD (uMRD) after CIT is a prognostic factor irrespective of clinical response, while residual lymphadenopathy seemed to be associated with inferior outcome [3]. Pretreatment lymphadenopathy has been associated with earlier progression and inferior treatment outcomes, however data on posttreatment lymphadenopathy is lacking [4,5,6,7]. The analysis presented here aims to determine the prognostic value of residual lymphadenopathy in patients with or without uMRD after chemoimmunotherapy.

We included 361 patients receiving frontline CIT within three prospective clinical trials of the German CLL Study Group (CLL2M: 23 patients, CLL8: 113 patients, and CLL10: 225 patients) with available radiological assessment of abdominal lymphadenopathy at the time point of final restaging 2 months after the end of last treatment cycle [1, 8, 9]. CT scans at final restaging were recommended for all patients but were not mandatory. Of the 361 patients included in this analysis, 227 (62.9%) received fludarabine, cyclophosphamide, and rituximab (FCR) and 134 (37.1%) patients received bendamustine and rituximab (BR) (Fig. S1). Abdominal lymphadenopathy was selected as an exemplary manifestation of residual disease in the lymph node compartment, an additional subgroup analysis was done for patients with any enlarged lymph nodes at final restaging (Supplementary material).

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Acknowledgements

We wish to thank the patients and their treating physicians who participated in the trials. The data have not been previously published or submitted for publication. Parts of the data have been presented as a poster at the 60th ASH annual meeting 2018 in San Diego. The CLL2M and CLL10 trials were conducted as investigator-initiated trials by the German Chronic Lymphocytic Leukemia Study Group (GCLLSG). They were supported by research grants from Roche Pharma AG, and Mundipharma and a grant from the German Federal Ministry of Education. The CLL8 study was conducted as an investigator-initiated trial by the GCLLSG from 2003 to 2004 and afterwards sponsored by F. Hoffmann-La Roche.

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Authors and Affiliations

  1. Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German CLL Study Group, University Hospital Cologne, University of Cologne, Cologne, Germany

    M. Fürstenau, J. Bahlo, A. M. Fink, K. Fischer, M. Hallek & B. Eichhorst

  2. Evangelisches Krankenhaus Hamm, Hamm, Germany

    E. Lange

  3. Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany

    P. Dreger

  4. Department of Internal Medicine III, University Hospital of the Ludwig Maximilians University Munich, Munich, Germany

    M. Dreyling

  5. Department of Hematology, Medical Oncology and Pneumology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

    G. Hess

  6. Department II of Internal Medicine, University of Schleswig-Holstein, Kiel, Germany

    M. Ritgen, M. Kneba & S. Böttcher

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

    H. Döhner & S. Stilgenbauer

  8. Department of Hematology, Oncology and Rheumatology and José Carreras Center for Immuno and Gene Therapy, Saarland University Medical School, Homburg/Saar, Germany

    S. Stilgenbauer

  9. Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, München Klinik Schwabing, Munich, Germany

    C. M. Wendtner

  10. Oncogeriatric Unit, Department of Geriatric Medicine, St. Marien Hospital, Cologne, Germany

    V. Goede

  11. Medical Clinic III, Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, Rostock, Germany

    S. Böttcher

  12. Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Disease (CECAD), University of Cologne, Cologne, Germany

    M. Hallek

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  1. M. Fürstenau
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  2. J. Bahlo
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Correspondence to M. Fürstenau or B. Eichhorst.

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Conflict of interest

MF, EL, and PD declare that they have no competing interests. JB reports personal fees (travel support) from Roche. AMF reports personal fees (advisory board) from Janssen Pharmaceutical during the conduct of the study. MD reports personal fees from Acerta, Bayer, Gilead, Novartis, Sandoz, grants and personal fees from Celgene, Janssen, Roche, and grants from Mundipharma outside the submitted work. DGH reports personal fees from Janssen, grants and personal fees from Roche, personal fees from Abbvie, personal fees from Gilead, personal fees from Novartis, grants from Pfizer, personal fees from Morphosys, and grants and personal fees from Celgene. MR reports grants from Roche during the conduct of the study, and personal fees from Roche outside the submitted work. MK reports personal fees from Roche and AbbVie. SS reports grants, personal fees, and nonfinancial support from AbbVie, grants, personal fees, and nonfinancial support from Amgen, grants, personal fees, and nonfinancial support from AstraZeneca, grants, personal fees, and nonfinancial support from Celgene, grants, personal fees, and nonfinancial support from Gilead, grants, personal fees, and nonfinancial support from GSK, grants, personal fees, and nonfinancial support from Hoffmann-La Roche, grants, personal fees, and nonfinancial support from Janssen, grants, personal fees, and nonfinancial support from Novartis, grants, personal fees, and nonfinancial support from Pharmacyclics, and grants, personal fees, and nonfinancial support from Sunesis outside the submitted work. HD reports personal fees from Agios, AbbVie, Amgen, Astellas, Astex, Celator, Celgene, Janssen, Jazz, Novartis, Seattle Genetics, and Sunesis and research funding from AROG, Bristol Myers Squibb, Celgene, Novartis, Pfizer, and Sunesis. CMW reports grants and personal fees from Hoffmann-La Roche, grants and personal fees from Mundipharma during the conduct of the study, grants and personal fees from Hoffmann-La Roche, grants and personal fees from Mundipharma, grants and personal fees from Janssen-Cilag, grants and personal fees from AbbVie, grants and personal fees from Gilead, grants and personal fees from Novartis, grants and personal fees from Celgene, and grants and personal fees from MorphoSys outside the submitted work. VG reports personal fees from Roche, personal fees from Janssen, personal fees from Gilead, personal fees from AbbVie, outside the submitted work. KF reports personal fees (travel support) from Roche. SB reports personal fees from Roche, AbbVie, Janssen, research funding from Roche, AbbVie, Celgene, Genentech, and appeared on an advisory board for Roche. MH reports research grants from Roche, Gilead, Mundipharma, Janssen, Celgene, Pharmacyclics, and Abbvie. Speakers bureau and Advisory Board for Roche, Gilead, Mundipharma, Janssen, Celgene, Pharmacyclics, Boehringer. BE reports research grants from Abbvie, Gilead, Janssen, Roche, and Beigene and personal fees, advisory boards from the same companies and Celgene and Novartis in addition.

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Fürstenau, M., Bahlo, J., Fink, A.M. et al. Residual abdominal lymphadenopathy after intensive frontline chemoimmunotherapy is associated with inferior outcome independently of minimal residual disease status in chronic lymphocytic leukemia. Leukemia 34, 924–928 (2020). https://doi.org/10.1038/s41375-019-0597-3

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