期刊
JOURNAL OF IMMUNOTHERAPY
卷 41, 期 3, 页码 151-157出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0000000000000220
关键词
ofatumumab; CD20; IL-18; IFN-; lymphoma
资金
- NIH [P30 CA82709, RO1 CA118118]
- Indiana University Health-Indiana University School of Medicine Strategic Research Initiative
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 1000mg 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 30g/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 30g/kg cohorts, respectively. Serum concentrations of interferon- 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.
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