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Lymphoma

Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma

Leukemia volume 26, pages 1046–1052 (2012)Cite this article

Abstract

Follicular lymphoma exhibits intratumoral infiltration by non-malignant T lymphocytes, including CD4+CD25+ regulatory T (Treg) cells. We combined denileukin diftitox with rituximab in previously untreated, advanced-stage follicular lymphoma patients anticipating that denileukin diftitox would deplete CD25+ Treg cells while rituximab would deplete malignant B cells. Patients received rituximab 375 mg/m2 weekly for 4 weeks and denileukin diftitox 18 mcg/kg/day for 5 days every 3 weeks for 4 cycles; neither agent was given as maintenance therapy. Between August 2008 and March 2010, 24 patients were enrolled. One patient died before treatment was given and was not included in the analysis. Eleven of 23 patients (48%; 95% confidence interval (CI): 27–69%) responded; 2 (9%) had complete responses and 9 (39%) had partial responses. The progression-free rate at 2 years was 55% (95%CI: 37–82%). Thirteen patients (57%) experienced grade ⩾3 adverse events and one patient (4%) died. In correlative studies, soluble CD25 and the number of CD25+ T cells decreased after treatment; however, there was a compensatory increase in IL-15 and IP-10. We conclude that although the addition of denileukin diftitox to rituximab decreased the number of CD25+ T cells, denileukin diftitox contributed to the toxicity of the combination without an improvement in response rate or time to progression.

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Acknowledgements

This work was supported in part by grants CA92104 and CA25224 from the National Institutes of Health and the Predolin Foundation.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    S M Ansell, G S Nowakowski, Z Yang, D M Grote, S C Ziesmer & T E Witzig

  2. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

    H Tang & G D Nelson

  3. Division of Hematopathology, Mayo Clinic, Rochester, MN, USA

    P J Kurtin

  4. North Central Cancer Treatment Group, Rochester, MN, USA

    P A Koenig, D A Nikcevich, P T Silberstein & C Erlichman

Authors
  1. S M Ansell
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  2. H Tang
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  3. P J Kurtin
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  4. P A Koenig
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  5. G S Nowakowski
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  6. D A Nikcevich
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  8. Z Yang
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  10. S C Ziesmer
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  13. T E Witzig
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Corresponding author

Correspondence to S M Ansell.

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Competing interests

SMA received research funding from Eisai Inc. for this study. The remaining authors declare no conflict of interest.

Additional information

Presented in part at the 52nd Annual Meeting of the American Society of Hematology.

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Ansell, S., Tang, H., Kurtin, P. et al. Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma. Leukemia 26, 1046–1052 (2012). https://doi.org/10.1038/leu.2011.297

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