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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

Fingerprint

Peripheral Blood Stem Cell Transplantation
Interleukin-18
Lymphoma
Intravenous Infusions
Natural Killer Cells
Monoclonal Antibodies
Maximum Tolerated Dose
Antibodies
B-Cell Lymphoma
Chemokines
Human Activities
Interferons
ofatumumab
Blood Cells
B-Lymphocytes
Animal Models
Cytokines
Drug Therapy
Serum
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination with Ofatumumab after Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma. / Robertson, Michael; Stamatkin, Christopher W.; Pelloso, David; Weisenbach, Jill; Prasad, Nagendra K.; Safa, Ahmad.

In: Journal of Immunotherapy, Vol. 41, No. 3, 01.01.2018, p. 151-157.

Research output: Contribution to journalArticle

@article{3c498f5ddf4a474e92d1d945e83896ae,
title = "A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination with Ofatumumab after Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma",
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.",
keywords = "CD20, IFN-γ, IL-18, lymphoma, ofatumumab",
author = "Michael Robertson and Stamatkin, {Christopher W.} and David Pelloso and Jill Weisenbach and Prasad, {Nagendra K.} and Ahmad Safa",
year = "2018",
month = "1",
day = "1",
doi = "10.1097/CJI.0000000000000220",
language = "English (US)",
volume = "41",
pages = "151--157",
journal = "Journal of Immunotherapy",
issn = "1524-9557",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination with Ofatumumab after Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma

AU - Robertson, Michael

AU - Stamatkin, Christopher W.

AU - Pelloso, David

AU - Weisenbach, Jill

AU - Prasad, Nagendra K.

AU - Safa, Ahmad

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - CD20

KW - IFN-γ

KW - IL-18

KW - lymphoma

KW - ofatumumab

UR - http://www.scopus.com/inward/record.url?scp=85044376405&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044376405&partnerID=8YFLogxK

U2 - 10.1097/CJI.0000000000000220

DO - 10.1097/CJI.0000000000000220

M3 - Article

C2 - 29517616

AN - SCOPUS:85044376405

VL - 41

SP - 151

EP - 157

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

SN - 1524-9557

IS - 3

ER -