title: Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly-diagnosed, previously untreated multiple myeloma: an open-label phase I trial.
abstract: The safety and efficacy of siltuximab (CNTO 328) was tested in combination with lenalidomide, bortezomib and dexamethasone (RVD) in patients with newly-diagnosed, previously untreated symptomatic multiple myeloma. Fourteen patients were enrolled in the study, eleven of whom qualified to receive therapy. A majority of patients (81.8%) completed the minimal number or more of the four required cycles, while two patients completed only three cycles. The maximum tolerated dose (MTD) of siltuximab with RVD was dose level -1 (siltuximab: 8.3 mg/kg; bortezomib: 1.3 mg/m(2); lenalidomide: 25 mg; dexamethasone: 20 mg). Serious adverse events were grade 3 pneumonia and grade 4 thrombocytopenia, and no deaths occurred during the study or with follow-up (median follow-up 28.1 months). An overall response rate, after 3-4 cycles of therapy, of 90.9% (95% confidence interval (CI): 58.7%, 99.8%) (9.1% complete response (95% CI: 0.2%, 41.3%), 45.5% very good partial response (95% CI: 16.7%, 76.6%) and 36.4% partial response (95% CI: 10.9%, 69.2%)) was seen. Two patients withdrew consent, and nine patients (81.8%) opted for autologous stem cell transplantation.
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Shah
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Thomas
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Berkova
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Weber
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Qazilbash
authors.affiliation: Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Mendoza
authors.affiliation: Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Cleeland
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: R Z
authors.initials: RZ
authors.lastname: Orlowski
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage; D002869:Chromosome Aberrations; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D009367:Neoplasm Staging; D011788:Quality of Life; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide; C504234:siltuximab