title: A humanized HLA-DR antibody (hu1D10, apolizumab) in combination with granulocyte colony-stimulating factor (filgrastim) for the treatment of non-Hodgkin's lymphoma: a pilot study.
abstract: Apolizumab is a humanized monoclonal antibody against a polymorphic epitope on HLA DRbeta that demonstrated evidence for therapeutic activity in follicular lymphoma patients. In pre-clinical studies, we previously reported that granulocyte colony-stimulating factor (G-CSF) treatment significantly enhanced lymphoma cell killing by HLA class II antibodies, including apolizumab. These results suggested a combination trial of apolizumab and G-CSF (filgrastim). In this trial, we treated six patients with relapsed or refractory 1D10-positive non-Hodgkin's lymphoma with filgrastim and variable doses of apolizumab ranging from 0.15 to 1.5 mg/m2. The combination was clinically well tolerated, with only two patients experiencing grade III/IV hematological toxicity (thrombocytopenia and autoimmune hemolytic anemia). Another patient developed a pruritic skin rash, which was probably a treatment-related grade II skin toxicity. Interestingly, two patients with follicular lymphoma who received intensified apolizumab treatment on a three times weekly schedule experienced prolonged stabilization of their disease for 12 and more than 36 months. In conclusion, this small pilot study suggests that a combination of HLA class II antibodies and G-CSF is clinically feasible.
authors.affiliation: Department of Medicine III, University of Erlangen-Nueremberg, Germany. juergen@med3.imed.uni-erlangen.de
authors.forename: Juergen
authors.initials: J
authors.lastname: Rech
authors.forename: Roland
authors.initials: R
authors.lastname: Repp
authors.forename: Dorit
authors.initials: D
authors.lastname: Rech
authors.forename: Bernhard
authors.initials: B
authors.lastname: Stockmeyer
authors.forename: Michael
authors.initials: M
authors.lastname: Dechant
authors.forename: Gerald
authors.initials: G
authors.lastname: Niedobitek
authors.forename: Martin
authors.initials: M
authors.lastname: Gramatzki
authors.forename: Thomas
authors.initials: T
authors.lastname: Valerius
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C448699:apolizumab; D000069585:Filgrastim