@article{3110361,
    title = "A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma",
    author = "Orlowski, R.Z. and Gercheva, L. and Williams, C. and Sutherland, H. and Robak, T. and Masszi, T. and Goranova-Marinova, V. and Dimopoulos, M.A. and Cavenagh, J.D. and Špička, I. and Maiolino, A. and Suvorov, A. and Bladé, J. and Samoylova, O. and Puchalski, T.A. and Reddy, M. and Bandekar, R. and van de Velde, H. and Xie, H. and Rossi, J.-F.",
    journal = "American Journal of Hematology",
    year = "2015",
    volume = "90",
    number = "1",
    pages = "42-49",
    publisher = "Wiley-Liss, Inc.",
    issn = "0361-8609, 1096-8652",
    doi = "10.1002/ajh.23868",
    keywords = "alanine aminotransferase;  aspartate aminotransferase;  bortezomib;  C reactive protein;  colony stimulating factor;  dexamethasone;  hemoglobin;  interleukin 6;  lenalidomide;  placebo;  siltuximab;  triacylglycerol;  antineoplastic agent;  boronic acid derivative;  bortezomib;  IL6 protein, human;  interleukin 6;  monoclonal antibody;  pyrazine derivative;  siltuximab, adult;  aged;  alanine aminotransferase blood level;  anemia;  Article;  aspartate aminotransferase blood level;  bleeding;  blood transfusion;  bronchitis;  cancer combination chemotherapy;  cancer growth;  cancer patient;  cancer recurrence;  cancer survival;  constipation;  controlled study;  corticosteroid therapy;  decreased appetite;  diarrhea;  double blind procedure;  drug efficacy;  drug megadose;  drug safety;  drug withdrawal;  fatigue;  febrile neutropenia;  female;  follow up;  hemoglobin blood level;  human;  hypercholesterolemia;  hypertriglyceridemia;  major clinical study;  male;  maximum plasma concentration;  multiple cycle treatment;  multiple myeloma;  neuralgia;  neutropenia;  overall survival;  phase 2 clinical trial;  pneumonia;  priority journal;  progression free survival;  protein blood level;  randomized controlled trial;  rhinopharyngitis;  salvage therapy;  sensory neuropathy;  thrombocytopenia;  treatment duration;  treatment response;  triacylglycerol blood level;  upper respiratory tract infection;  clinical trial;  disease free survival;  immunology;  Kaplan Meier method;  middle aged;  mortality;  multiple myeloma;  recurrent disease;  very elderly, Adult;  Aged;  Aged, 80 and over;  Antibodies, Monoclonal;  Antineoplastic Combined Chemotherapy Protocols;  Boronic Acids;  Disease-Free Survival;  Double-Blind Method;  Female;  Humans;  Interleukin-6;  Kaplan-Meier Estimate;  Male;  Middle Aged;  Multiple Myeloma;  Pyrazines;  Recurrence",
    abstract = "We compared the safety and efficacy of siltuximab (S), an anti-interleukin-6 chimeric monoclonal antibody, plus bortezomib (B) with placebo (plc) + B in patients with relapsed/refractory multiple myeloma in a randomized phase 2 study. Siltuximab was given by 6 mg/kg IV every 2 weeks. On progression, B was discontinued and high-dose dexamethasone could be added to S/plc. Response and progression-free survival (PFS) were analyzed pre-dexamethasone by European Group for Blood and Marrow Transplantation (EBMT) criteria. For the 281 randomized patients, median PFS for S + B and plc + B was 8.0 and 7.6 months (HR 0.869, P = 0.345), overall response rate was 55 versus 47% (P = 0.213), complete response rate was 11 versus 7%, and median overall survival (OS) was 30.8 versus 36.8 months (HR 1.353, P = 0.103). Sustained suppression of C-reactive protein, a marker reflective of inhibition of interleukin-6 activity, was seen with S + B. Siltuximab did not affect B pharmacokinetics. Siltuximab/placebo discontinuation (75 versus 66%), grade ≥3 neutropenia (49 versus 29%), thrombocytopenia (48 versus 34%), and all-grade infections (62 versus 49%) occurred more frequently with S + B. The addition of siltuximab to bortezomib did not appear to improve PFS or OS despite a numerical increase in response rate in patients with relapsed or refractory multiple myeloma. © 2014 Wiley Periodicals, Inc."
}