title: A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma.
abstract: Interleukin-6 (IL6) plays a central role in multiple myeloma pathogenesis and confers resistance to corticosteroid-induced apoptosis. We therefore evaluated the efficacy and safety of siltuximab, an anti-IL6 monoclonal antibody, alone and in combination with dexamethasone, for patients with relapsed or refractory multiple myeloma who had ≥ 2 prior lines of therapy, one of which had to be bortezomib-based. Fourteen initial patients received siltuximab alone, 10 of whom had dexamethasone added for suboptimal response; 39 subsequent patients were treated with concurrent siltuximab and dexamethasone. Patients received a median of four prior lines of therapy, 83% were relapsed and refractory, and 70% refractory to their last dexamethasone-containing regimen. Suppression of serum C-reactive protein levels, a surrogate marker of IL6 inhibition, was demonstrated. There were no responses to siltuximab but combination therapy yielded a partial (17%) + minimal (6%) response rate of 23%, with responses seen in dexamethasone-refractory disease. The median time to progression, progression-free survival and overall survival for combination therapy was 4.4, 3.7 and 20.4 months respectively. Haematological toxicity was common but manageable. Infections occurred in 57% of combination-treated patients, including ≥ grade 3 infections in 18%. Further study of siltuximab in modern corticosteroid-containing myeloma regimens is warranted, with special attention to infection-related toxicity.
authors: Division of Hematology-Oncology, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599-7305, USA. peter_voorhees@med.unc.edu
authors: Peter M
authors: PM
authors: Voorhees
authors: Robert F
authors: RF
authors: Manges
authors: Pieter
authors: P
authors: Sonneveld
authors: Sundar
authors: S
authors: Jagannath
authors: George
authors: G
authors: Somlo
authors: Amrita
authors: A
authors: Krishnan
authors: Suzanne
authors: S
authors: Lentzsch
authors: Richard C
authors: RC
authors: Frank
authors: Sonja
authors: S
authors: Zweegman
authors: Pierre W
authors: PW
authors: Wijermans
authors: Robert Z
authors: RZ
authors: Orlowski
authors: Britte
authors: B
authors: Kranenburg
authors: Brett
authors: B
authors: Hall
authors: Tineke
authors: T
authors: Casneuf
authors: Xiang
authors: X
authors: Qin
authors: Helgi
authors: H
authors: van de Velde
authors: Hong
authors: H
authors: Xie
authors: Sheeba K
authors: SK
authors: Thomas
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology; D000069286:Bortezomib; D002097:C-Reactive Protein / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D017053:Infection Control; D015850:Interleukin-6 / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology; D016879:Salvage Therapy; D000093242:Interleukin-6 Inhibitors
chemical_list: D000305:Adrenal Cortex Hormones; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001897:Boronic Acids; D000069286:Bortezomib; D002097:C-Reactive Protein; D003907:Dexamethasone; D015850:Interleukin-6; D011719:Pyrazines; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C504234:siltuximab