IL-2-based immunotherapy after authologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: A phase I/II trial

L. J. Burns, D. J. Weisdorf, T. E. DeFor, D. H. Vesole, T. L. Repka, B. R. Blazar, S. R. Burger, A. Panoskaltsis-Mortari, C. A. Keever-Taylor, M. J. Zhang, J. S. Miller

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

We determined the safety, immune activating effects, and potential efficacy of i.v. infusion of ex vivo interleukin-2 (IL-2) activated natural killer (NK) cells (part I) or IL-2 boluses (part II) during daily s.c. IL-2 administration following hematopoietic recovery from autologous transplantation. In all, 57 patients with relapsed lymphoma (n = 29) or metastatic breast cancer (n = 28) were enrolled. In part I of the study, 34 patients were enrolled at three dose levels of ex vivo IL-2-activated NK cells. Lymphaphereses were performed on days 28 and 42 of s.c. IL-2 administration. Following overnight ex vivo IL-2 activation of the pheresis product, the cells were reinfused the following day. In part II, 23 patients were enrolled at three dose levels of supplemental i.v. IL-2 bolus infusions, given on days 28 and 35 during s.c. IL-2 administration. Toxicities were generally mild, and no patient required hospitalization. Lytic function was markedly enhanced for fresh peripheral blood mononuclear cells (PBMNCs) obtained 1 day postinfusion of either IL-2-activated cells or IL-2 boluses. IL-2 boluses transiently increased the levels of IL-6, IFN-γ, TNF-α and IL1-β, with increases in IL-6 and IFN-γ being dose dependent. A total of 37 patients (19 patients with lymphoma, 18 with breast cancer) treated with an optimum dose of post-transplant immunotherapy (defined as having received 1.75 × 106 IU/m2/day of s.c. IL-2 plus at least one of the planned ex vivo IL-2-activated cell infusions/IL-2 boluses) could be matched with controls from the Autologous Blood and Marrow Transplant Registry database. The matched-pairs analysis demonstrated no improvement in disease outcomes of survival and relapse. We conclude that IL-2-activated cells/IL-2 boluses can be safely administered, generate PBMNCs with enhanced cytotoxicity against NK-resistant targets, and increase cytokine levels. With this dose and schedule of administration of IL-2, no improvement in patient disease outcomes was noted. Alternative strategies will be needed to exploit the immunotherapeutic potential of IL-2-activated NK cells.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalBone marrow transplantation
Volume32
Issue number2
DOIs
StatePublished - Jul 2003

Keywords

  • IL-2
  • Immunotherapy
  • NK cells

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