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First-line treatment with R-CHOP or rituximab-bendamustine in patients with follicular lymphoma grade 3A—results of a retrospective analysis

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Abstract

Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P < 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.

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Availability of data and material

The datasets generated and analyzed during the current study are not publicly available due to personal data protection reasons but are available from the corresponding author on reasonable request.

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Author information

Authors and Affiliations

  1. Department of Hematology, Oncology and Rheumatology, Universitätsklinikum Heidelberg, Heidelberg, Germany

    M. Pouyiourou, J. Meissner & M. Witzens-Harig

  2. Department of Hematology and Oncology, Vivantes Klinikum Am Urban, Dieffenbachstraße 1, 10967, Berlin, Germany

    M. Pouyiourou & Christian W. Scholz

  3. Department of Hematology, Oncology and Tumor Immunology, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

    A. Meyer & U. Keller

  4. Institut for Medical Biometrics and Clinical Epidemiology, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

    A. Stroux

  5. Department of Hematology, Oncology, Palliative Care, Rheumatology and Infectious Diseases, Universitätsklinikum Ulm, Ulm, Germany

    A. Viardot

  6. Department of Oncology, Hematology, Immunology, Infectious Diseases and Palliative Care, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen, Germany

    P. La Rosée

  7. Department of Hematology and Medical Oncology, Universitätsklinikum Jena, Jena, Germany

    P. La Rosée

  8. Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany

    G. Maschmeyer

  9. Medical Practice for Hematology and Oncology, Outpatient Chemotherapy and Palliative Care, Lüdenscheid, Germany

    D. Kämpfe

  10. Department of Hematology, Oncology and Palliative Care, Klinikum Magdeburg, Magdeburg, Germany

    C. Kahl

  11. Department of Hematology and Cell Therapy, Medical Oncology, Hemostaseology, Leipzig, Germany

    V. Vucinic

  12. Institute of Pathology, Universitätsklinikum Leipzig, Leipzig, Germany

    A. Monecke

  13. Department of Hematology and Oncology, Transplantation Centre and Palliative Care, Universitätsmedizin Greifswald, Greifswald, Germany

    C. Hirt

  14. Department of Hematology and Oncology, Universitätsklinikum Halle (Saale), Halle (Saale), Germany

    T. Weber

  15. Department of Hematology, Oncology and Palliative Care, Universitätsmedizin Rostock, Rostock, Germany

    S. Böttcher

  16. Department of Hematology, Medical Oncology and Palliative Care, Städtisches Klinikum Dresden, Dresden, Germany

    H. Schmalenberg

  17. Department of Hematology, Oncology and Stem Cell Transplantation, Universitätsklinikum Freiburg, Freiburg, Germany

    R. Marks

  18. Onkopraxis Dresden, Dresden, Germany

    G. Prange-Krex

  19. Department of Hematology and Oncology, Universitätsklinikum Carl Gustav Carus, Dresden, Germany

    F. Kroschinsky

  20. Department of Hematology and Oncology, Klinikum rechts der Isar der Technischen Universität München, München, Germany

    E. Hauf & U. Keller

  21. Department of Hematopathology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany

    K. Koch & W. Klapper

  22. Oncological Center, Helios Klinikum Erfurt, Erfurt, Germany

    M. Herold

Authors
  1. M. Pouyiourou
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  2. A. Meyer
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  3. A. Stroux
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  4. A. Viardot
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  5. P. La Rosée
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  8. C. Kahl
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  25. Christian W. Scholz
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Consortia

on behalf of the East German Study Group for Hematology and Oncology (OSHO)

Contributions

MP collected and analyzed the data and wrote the first draft of the manuscript. AM, AV, PLR, GM, CH, TW, MWH, SB, MH, DK, CK, VV, AM, JM, HS, RM, GPK, FK, EH, and UK collected the data. AS guided the statistical analysis. KK and WK performed the reference pathology. All authors commented on previous versions of the manuscript and revised the paper critically. CWS designed the research, overlooked the study, commented on previous versions of the manuscript, and revised the paper critically.

Corresponding author

Correspondence to Christian W. Scholz.

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Conflict of interest

AV has been on Advisory Boards for Amgen, Roche, Kite/Gilead, and Novartis and received travel support and speaker honoraria from Amgen, Roche, Kite/Gilead, and Janssen. PLR has been on the Advisory Board for Roche. GM has received honoraria for lectures from Gilead, Janssen Cilag, AMGEN, Merck-Serono, Bristol-Myers Squibb, and AstraZeneca and travel grants from Janssen Cilag. TW has received travel grants and has been on the Advisory Board for Roche. SB reports consulting fees from Roche and AbbVie, research funding from Roche, Janssen, AbbVie, and Celgene, and honoraria from Roche, AbbVie, Janssen, Novartis, and Becton Dickinson. HS has received speaker honoraria and has been on the Advisory Boards for Lilly, MSD, Roche, Novartis, BMS, Basilea, Merck Serono, and Servier and has received research support from Sanofi. RM has received speaker honoraria and has been on the Advisory Boards for Janssen, Merck, Eusa, Novartis, and Kite/Gilead and has received travel grants from Kite/Gilead. UK has received travel support, speaker support and speaker honoraria from Roche and travel support and speaker honoraria from Mundipharma. WK has received research grants from Roche, Takeda, Amgen and Regeneron. SWS has received speaker honoraria from Gilead, Janssen and Pfizer and has been on the Advisory Boards for Roche, Novartis, Janssen, Hexal, Gilead, Takeda, Daiichi Sankyo, Celgene, Bristol-Myers Squibb, and Merck Serono. All remaining authors have declared no conflicts of interest.

Ethical approval

The retrospective analysis was approved by the ethics committee of the Berlin Chamber of Physicians. The study was conducted in accordance with Good Clinical Practice guidelines and the provisions of the Declaration of Helsinki.

Consent to participate

As this is a retrospective analysis of patient data, no additional informed consent was required. Patient data was collected and analyzed in anonymized form. Dates of birth were provided as five-year intervals in order to avoid patient identification (i.e., 1950–1954 for a patient born in 1952).

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Not applicable.

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Electronic supplementary material

Supplementary Fig. 1a

Kaplan-Meier plot of time-to-next treatment for patients with grade 3A or 1-2-3A FL with R-CHOP versus R-Bendamustine (DOCX 35 kb).

Supplementary Fig. 1b

Kaplan-Meier plot of time-to-next treatment for patients with grade 1-2 FL with R-CHOP versus R-Bendamustine (DOCX 39 kb).

Supplementary Table 1

(DOCX 15 kb).

Supplementary Table 2

(DOCX 15 kb).

Supplementary Table 3

(DOCX 15 kb).

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Pouyiourou, M., Meyer, A., Stroux, A. et al. First-line treatment with R-CHOP or rituximab-bendamustine in patients with follicular lymphoma grade 3A—results of a retrospective analysis. Ann Hematol 99, 2821–2829 (2020). https://doi.org/10.1007/s00277-020-04171-7

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