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

S. M. Ansell, H. Tang, P. J. Kurtin, P. A. Koenig, G. S. Nowakowski, D. A. Nikcevich, G. D. Nelson, Z. Yang, D. M. Grote, S. C. Ziesmer, P. T. Silberstein, C. Erlichman, T. E. Witzig

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Follicular lymphoma exhibits intratumoral infiltration by non-malignant T lymphocytes, including CD4CD25 regulatory T (T reg) cells. We combined denileukin diftitox with rituximab in previously untreated, advanced-stage follicular lymphoma patients anticipating that denileukin diftitox would deplete CD25 T reg 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.

Original languageEnglish (US)
Pages (from-to)1046-1052
Number of pages7
JournalLeukemia
Volume26
Issue number5
DOIs
StatePublished - May 2012

Keywords

  • Follicular lymphoma
  • denileukin diftitox
  • rituximab

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Ansell, S. M., Tang, H., Kurtin, P. J., Koenig, P. A., Nowakowski, G. S., Nikcevich, D. A., Nelson, G. D., Yang, Z., Grote, D. M., Ziesmer, S. C., Silberstein, P. T., Erlichman, C., & Witzig, T. E. (2012). Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma. Leukemia, 26(5), 1046-1052. https://doi.org/10.1038/leu.2011.297