A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma

作者：Voorhees Peter M^*; Manges Robert F; Sonneveld Pieter; Jagannath Sundar; Somlo George; Krishnan Amrita; Lentzsch Suzanne; Frank Richard C; Zweegman Sonja; Wijermans Pierre W; Orlowski Robert Z; Kranenburg Britte; Hall Brett; Casneuf Tineke; Qin Xiang; van de Velde Helgi; Xie Hong; Thomas Sheeba K

来源：British Journal of Haematology, 2013, 161(3): 357-366.

DOI：10.1111/bjh.12266

• interleukin-6
• siltuximab
• multiple myeloma
• dexamethasone
• targeted therapy

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 center dot 4, 3 center dot 7 and 20 center dot 4months 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.

• 出版日期2013-5