PMID- 29517616
OWN - NLM
STAT- MEDLINE
DCOM- 20190911
LR  - 20240213
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 41
IP  - 3
DP  - 2018 Apr
TI  - A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination With 
      Ofatumumab After Autologous Peripheral Blood Stem Cell Transplantation for 
      Lymphoma.
PG  - 151-157
LID - 10.1097/CJI.0000000000000220 [doi]
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 mug/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 mug/kg cohorts, 
      respectively. Serum concentrations of interferon-gamma 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.
FAU - Robertson, Michael J
AU  - Robertson MJ
AD  - Lymphoma Program and Bone Marrow and Stem Cell Transplantation Program, 
      Department of Medicine, Division of Hematology/Oncology.
FAU - Stamatkin, Christopher W
AU  - Stamatkin CW
AD  - Therapeutic Validation Core, Indiana University Simon Cancer Center.
FAU - Pelloso, David
AU  - Pelloso D
AD  - Lymphoma Program and Bone Marrow and Stem Cell Transplantation Program, 
      Department of Medicine, Division of Hematology/Oncology.
FAU - Weisenbach, Jill
AU  - Weisenbach J
AD  - Lymphoma Program and Bone Marrow and Stem Cell Transplantation Program, 
      Department of Medicine, Division of Hematology/Oncology.
FAU - Prasad, Nagendra K
AU  - Prasad NK
AD  - Therapeutic Validation Core, Indiana University Simon Cancer Center.
FAU - Safa, Ahmad R
AU  - Safa AR
AD  - Therapeutic Validation Core, Indiana University Simon Cancer Center.
AD  - Department of Pharmacology and Toxicology, Indiana University School of Medicine, 
      Indianapolis, IN.
LA  - eng
GR  - UL1 RR025761/RR/NCRR NIH HHS/United States
GR  - P30 CA082709/CA/NCI NIH HHS/United States
GR  - UL1 TR001108/TR/NCATS NIH HHS/United States
GR  - R01 CA118118/CA/NCI NIH HHS/United States
GR  - UL1 TR002529/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Cytokines)
RN  - 0 (IL18 protein, human)
RN  - 0 (Interleukin-18)
RN  - M95KG522R0 (ofatumumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/administration & dosage/pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Combined Modality Therapy
MH  - Cytokines/blood/metabolism
MH  - Female
MH  - Humans
MH  - Interleukin-18/administration & dosage/pharmacokinetics
MH  - Lymphocytes/drug effects/metabolism
MH  - Lymphoma/mortality/pathology/*therapy
MH  - Male
MH  - Middle Aged
MH  - Peripheral Blood Stem Cell Transplantation/methods
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC5847481
MID - NIHMS945776
COIS- Conflicts of Interest All other authors have declared that there are no financial 
      conflicts of interest in regard to this work.
EDAT- 2018/03/09 06:00
MHDA- 2019/09/12 06:00
PMCR- 2019/04/01
CRDT- 2018/03/09 06:00
PHST- 2018/03/09 06:00 [pubmed]
PHST- 2019/09/12 06:00 [medline]
PHST- 2018/03/09 06:00 [entrez]
PHST- 2019/04/01 00:00 [pmc-release]
AID - 10.1097/CJI.0000000000000220 [doi]
PST - ppublish
SO  - J Immunother. 2018 Apr;41(3):151-157. doi: 10.1097/CJI.0000000000000220.