A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination with Ofatumumab after Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma

Michael J. Robertson, Christopher W. Stamatkin, David Pelloso, Jill Weisenbach, Nagendra K. Prasad, Ahmad R. Safa

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Interleukin-18 (IL-18) is an immunostimulatory cytokine that augments antibody-dependent cellular cytotoxicity mediated by human natural killer cells against antibody-coated lymphoma cells in vitro and that has antitumor activity in animal models. Ofatumumab is a CD20 monoclonal antibody with activity against human B-cell lymphomas. A phase I study of recombinant human (rh) IL-18 given with ofatumumab was undertaken in patients with CD20 + lymphoma who had undergone high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Cohorts of 3 patients were given intravenous infusions of ofatumumab 1000 mg weekly for 4 weeks with escalating doses of rhIL-18 as a intravenous infusion weekly for 8 consecutive weeks. Nine male patients with CD20 + lymphomas were given ofatumumab in combination with rhIL-18 at doses of 3, 10, and 30 μg/kg. No unexpected or dose-limiting toxicities were observed. The mean reduction from predose levels in the number of peripheral blood natural killer cells after the first rhIL-18 infusion was 91%, 96%, and 97% for the 3, 10, and 30 μg/kg cohorts, respectively. Serum concentrations of interferon-γ and chemokines transiently increased following IL-18 dosing. rhIL-18 can be given in biologically active doses by weekly infusions in combination with ofatumumab after peripheral blood stem cell transplantation to patients with lymphoma. A maximum tolerated dose of rhIL-18 plus ofatumumab was not determined. Further studies of rhIL-18 and CD20 monoclonal antibodies in B-cell malignancies are warranted.

Original languageEnglish (US)
Pages (from-to)151-157
Number of pages7
JournalJournal of Immunotherapy
Volume41
Issue number3
DOIs
StatePublished - Jan 1 2018

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Keywords

  • CD20
  • IFN-γ
  • IL-18
  • lymphoma
  • ofatumumab

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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