• 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, and Sheeba K Thomas.
• Division of Hematology-Oncology, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599-7305, USA. peter_voorhees@med.unc.edu
• Br. J. Haematol. 2013 May 1;161(3):357-66.

AbstractInterleukin-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.© 2013 Blackwell Publishing Ltd.

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