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: Peter M Voorhees, Robert F Manges, Pieter Sonneveld, Sundar Jagannath, George Somlo, Amrita Krishnan, Suzanne Lentzsch, Richard C Frank, Sonja Zweegman, Pierre W Wijermans, Robert Z Orlowski, Britte Kranenburg, Brett Hall, Tineke Casneuf, Xiang Qin, Helgi van de Velde, Hong Xie, Sheeba K Thomas
• Journal: British journal of haematology (Br J Haematol) Vol. 161 Issue 3 Pg. 357-66 (May 2013) ISSN: 1365-2141 [Electronic] England
• PMID: 23432640 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2013 Blackwell Publishing Ltd.

Chemical References

• Adrenal Cortex Hormones
• Antibodies, Anti-Idiotypic
• Antibodies, Monoclonal
• Antineoplastic Agents
• Boronic Acids
• IL6 protein, human
• Interleukin-6
• Pyrazines
• Bortezomib
• Dexamethasone
• C-Reactive Protein
• siltuximab

Topics

• Adrenal Cortex Hormones (administration & dosage, pharmacology)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Anti-Idiotypic (biosynthesis)
• Antibodies, Monoclonal (administration & dosage, adverse effects, immunology, therapeutic use)
• Antineoplastic Agents (adverse effects, pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Boronic Acids (administration & dosage, pharmacology)
• Bortezomib
• C-Reactive Protein (analysis)
• Dexamethasone (administration & dosage)
• Disease Progression
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Female
• Hematologic Diseases (chemically induced)
• Humans
• Infection Control
• Interleukin-6 (antagonists & inhibitors, immunology)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multiple Myeloma (blood, drug therapy)
• Pyrazines (administration & dosage, pharmacology)
• Salvage Therapy