PMID- 23799412
OWN - NLM
STAT- MEDLINE
DCOM- 20140116
LR  - 20211021
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 36
IP  - 6
DP  - 2013 Jul-Aug
TI  - A dose-escalation study of recombinant human interleukin-18 in combination with 
      rituximab in patients with non-Hodgkin lymphoma.
PG  - 331-41
LID - 10.1097/CJI.0b013e31829d7e2e [doi]
AB  - Interleukin-18 (IL-18) is an immunostimulatory cytokine with antitumor activity 
      in preclinical models. Rituximab is a CD20 monoclonal antibody with activity 
      against human B-cell lymphomas. A phase I study of recombinant human (rh) IL-18 
      given with rituximab was performed in patients with CD20+ lymphoma. Cohorts of 
      3-4 patients were given infusions of rituximab (375 mg/m2) weekly for 4 weeks 
      with escalating doses of rhIL-18 as a 2-hour intravenous infusion weekly for 12 
      consecutive weeks. Toxicities were graded using standard criteria. Blood samples 
      were obtained for safety, pharmacokinetic, and pharmacodynamic studies. Nineteen 
      patients with CD20+ B-cell non-Hodgkin lymphoma were given rituximab in 
      combination with rhIL-18 at doses of 1, 3, 10, 20, 30, and 100 mug/kg. Common side 
      effects included chills, fever, headache, and nausea. Common laboratory 
      abnormalities included transient, asymptomatic lymphopenia, hyperglycemia, 
      anemia, hypoalbuminemia, and bilirubin and liver enzyme elevations. No 
      dose-limiting toxicities were observed. Biologic effects of rhIL-18 included 
      transient lymphopenia and increased expression of activation antigens on 
      lymphocytes. Increases in serum concentrations of IFN-gamma, GM-CSF, and chemokines 
      were observed after dosing. Objective tumor responses were seen in 5 patients, 
      including 2 complete and 3 partial responses. rhIL-18 can be given in 
      biologically active doses by weekly infusions in combination with rituximab to 
      patients with lymphoma. A maximum tolerated dose of rhIL-18 plus rituximab 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  - Department of Medicine, Division of Hematology/Oncology, Lymphoma Program, 
      Indiana University School of Medicine, Indianapolis, IN 46202, USA. 
      mjrobert@iupui.edu
FAU - Kline, Justin
AU  - Kline J
FAU - Struemper, Herbert
AU  - Struemper H
FAU - Koch, Kevin M
AU  - Koch KM
FAU - Bauman, John W
AU  - Bauman JW
FAU - Gardner, Olivia S
AU  - Gardner OS
FAU - Murray, Sharon C
AU  - Murray SC
FAU - Germaschewski, Fiona
AU  - Germaschewski F
FAU - Weisenbach, Jill
AU  - Weisenbach J
FAU - Jonak, Zdenka
AU  - Jonak Z
FAU - Toso, John F
AU  - Toso JF
LA  - eng
GR  - UL1 RR025761/RR/NCRR NIH HHS/United States
GR  - UL RR025761/RR/NCRR NIH HHS/United States
GR  - P30 CA082709/CA/NCI NIH HHS/United States
GR  - P30 CA82709/CA/NCI NIH HHS/United States
GR  - R01 CA118118/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antibodies, Monoclonal, Murine-Derived)
RN  - 0 (Interleukin-18)
RN  - 4F4X42SYQ6 (Rituximab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Murine-Derived/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Interleukin-18/*administration & dosage/adverse effects/pharmacokinetics
MH  - Lymphoma, Non-Hodgkin/*drug therapy/immunology
MH  - Male
MH  - Middle Aged
MH  - Rituximab
MH  - Treatment Outcome
PMC - PMC3770482
MID - NIHMS498725
EDAT- 2013/06/27 06:00
MHDA- 2014/01/17 06:00
PMCR- 2014/07/01
CRDT- 2013/06/27 06:00
PHST- 2013/06/27 06:00 [entrez]
PHST- 2013/06/27 06:00 [pubmed]
PHST- 2014/01/17 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - 00002371-201307000-00001 [pii]
AID - 10.1097/CJI.0b013e31829d7e2e [doi]
PST - ppublish
SO  - J Immunother. 2013 Jul-Aug;36(6):331-41. doi: 10.1097/CJI.0b013e31829d7e2e.