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Possible hampered effectiveness of second-line treatment with rituximab-containing chemotherapy without signs of rituximab resistance: a population-based study among patients with chronic lymphocytic leukemia

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Abstract

Rituximab-containing chemotherapy remains a viable frontline treatment option for patients with chronic lymphocytic leukemia (CLL) in the era of novel agents. However, its effectiveness in the second-line setting—in relation to previous rituximab exposure in first-line—has hardly been evaluated in a population-based setting. Therefore, in this comprehensive, population-based study, we assessed the impact of first-line treatment with rituximab-containing chemotherapy on the effectiveness of second-line treatment with rituximab-containing chemotherapy. We selected all 1735 patients diagnosed with CLL between 2004 and 2010 from the Dutch Population-based HAematological Registry for Observational Studies (PHAROS). The primary endpoint was treatment-free survival (TFS). First- and second-line treatment was instituted in 663 (38%) and 284 (43%) patients, respectively. In first line, the median TFS was 19.7 and 67.1 months for chemotherapy without (n = 445; 67%) and with rituximab (n = 218; 33%), respectively (adjusted hazard ratio [HRadjusted], 0.83; P = 0.031). The median TFS among recipients of second-line chemotherapy without (n = 165; 57%) and with rituximab (n = 121; 42%) was 15.0 and 15.3 months, respectively (HRadjusted, 0.93; P = 0.614). Of the 121 patients who received rituximab-containing chemotherapy in second-line, 89 (74%) and 32 (26%) received first-line chemotherapy without and with rituximab, respectively. Median TFS in these two treatment groups was 18.3 and 12.1 months, respectively (HRadjusted, 1.71; P = 0.060). Collectively, in this population-based study, the effectiveness of first-line treatment with rituximab-containing chemotherapy was less pronounced in second-line treatment. The hampered effectiveness of rituximab-containing chemotherapy in second-line could not be explained by previous rituximab exposure.

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Acknowledgments

The Population-based HAematological Registry for Observational Studies (PHAROS) is an initiative of the Haemato-Oncology Foundation for Adults in The Netherlands (HOVON), the institute of Medical Technology Assessment (iMTA) at the Erasmus University Rotterdam, and the Netherlands Comprehensive Cancer Organisation (IKNL). We are grateful to all participating centers, hematologists, research nurses, and data managers for their contributions and efforts that allowed for additional data collection.

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Author notes

  1. Avinash G. Dinmohamed and Mark-David Levin contributed equally to this work.

Authors and Affiliations

  1. Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands

    Lina van der Straten & Avinash G. Dinmohamed

  2. Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands

    Lina van der Straten & Mark-David Levin

  3. Amsterdam UMC, Department of Hematology, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands

    Arnon P. Kater & Avinash G. Dinmohamed

  4. Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands

    Jeanette K. Doorduijn

  5. PALGA Foundation, Houten, The Netherlands

    Esther C. van den Broek

  6. Department of Internal Medicine, Reinier de Graaf Hospital, Delft, The Netherlands

    Eduardus F.M. Posthuma

  7. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    Eduardus F.M. Posthuma

  8. Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands

    Avinash G. Dinmohamed

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  1. Lina van der Straten
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Contributions

LvdS, AGD, and M-DL designed the study; LvdS analyzed the data; AGD provided statistical support; ECvdB collected the data; LvdS wrote the manuscript with contributions from all authors, who also interpreted the data, and read, commented on, and approved the final version of the manuscript.

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Correspondence to Lina van der Straten.

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van der Straten, L., Kater, A.P., Doorduijn, J.K. et al. Possible hampered effectiveness of second-line treatment with rituximab-containing chemotherapy without signs of rituximab resistance: a population-based study among patients with chronic lymphocytic leukemia. Ann Hematol 99, 1081–1091 (2020). https://doi.org/10.1007/s00277-020-03994-8

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