TY - JOUR
TI - 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
AU - Orlowski, R.Z.
AU - Gercheva, L.
AU - Williams, C.
AU - Sutherland, H.
AU - Robak, T.
AU - Masszi, T.
AU - Goranova-Marinova, V.
AU - Dimopoulos, M.A.
AU - Cavenagh, J.D.
AU - Špička, I.
AU - Maiolino, A.
AU - Suvorov, A.
AU - Bladé, J.
AU - Samoylova, O.
AU - Puchalski, T.A.
AU - Reddy, M.
AU - Bandekar, R.
AU - van de Velde, H.
AU - Xie, H.
AU - Rossi, J.-F.
JO - American Journal of Hematology
PY - 2015
VL - 90
TODO - 1
SP - 42-49
PB - Wiley-Liss, Inc.
SN - 0361-8609, 1096-8652
TODO - 10.1002/ajh.23868
TODO - 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
TODO - 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.
ER -