A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma
| Autor: | Pierre W. Wijermans, Hong Xie, Peter M. Voorhees, Richard C. Frank, Robert Z. Orlowski, Brett Hall, Britte Kranenburg, Helgi van de Velde, Amrita Krishnan, Xiang Qin, Sonja Zweegman, Robert F. Manges, Sundar Jagannath, George Somlo, Tineke Casneuf, Suzanne Lentzsch, Sheeba K. Thomas, Pieter Sonneveld |
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| Přispěvatelé: | Hematology, CCA - Innovative therapy |
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Combination therapy Salvage therapy Antineoplastic Agents Kaplan-Meier Estimate Pharmacology Siltuximab Article Dexamethasone Drug Administration Schedule Bortezomib chemistry.chemical_compound Refractory Adrenal Cortex Hormones Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Multiple myeloma Aged Aged 80 and over Salvage Therapy Infection Control business.industry Interleukin-6 Antibodies Monoclonal Hematology Middle Aged medicine.disease Boronic Acids Hematologic Diseases Antibodies Anti-Idiotypic Regimen C-Reactive Protein chemistry Drug Resistance Neoplasm Pyrazines Disease Progression Female business Multiple Myeloma medicine.drug |
| Zdroj: | British Journal of Haematology, 161(3), 357-366. Wiley-Blackwell Publishing Ltd British Journal of Haematology, 161(3), 357-366. Wiley-Blackwell Voorhees, P M, Manges, R F, Sonneveld, P, Jagannath, S, Somlo, G, Krishnan, A, Lentzsch, S, Frank, R C, Zweegman, S, Wijermans, P W, Orlowski, R Z, Kranenburg, B, Hall, B, Casneuf, T, Qin, X, te Velde, H, Xie, H & Thomas, S K 2013, ' A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma ', British Journal of Haematology, vol. 161, no. 3, pp. 357-366 . https://doi.org/10.1111/bjh.12266 |
| ISSN: | 1365-2141 0007-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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