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.
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.
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Liana
authors.initials: L
authors.lastname: Gercheva
authors.forename: Cathy
authors.initials: C
authors.lastname: Williams
authors.forename: Heather
authors.initials: H
authors.lastname: Sutherland
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Tamás
authors.initials: T
authors.lastname: Masszi
authors.forename: Vesselina
authors.initials: V
authors.lastname: Goranova-Marinova
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: James D
authors.initials: JD
authors.lastname: Cavenagh
authors.forename: Ivan
authors.initials: I
authors.lastname: Špička
authors.forename: Angelo
authors.initials: A
authors.lastname: Maiolino
authors.forename: Alexander
authors.initials: A
authors.lastname: Suvorov
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Olga
authors.initials: O
authors.lastname: Samoylova
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Puchalski
authors.forename: Manjula
authors.initials: M
authors.lastname: Reddy
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bandekar
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Jean-Franςois
authors.initials: JF
authors.lastname: Rossi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence
chemical_list: D000911:Antibodies, Monoclonal; D001897:Boronic Acids; C508600:IL6 protein, human; D015850:Interleukin-6; D011719:Pyrazines; D000069286:Bortezomib; C504234:siltuximab