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: Robert Z Orlowski, Liana Gercheva, Cathy Williams, Heather Sutherland, Tadeusz Robak, Tamás Masszi, Vesselina Goranova-Marinova, Meletios A Dimopoulos, James D Cavenagh, Ivan Špička, Angelo Maiolino, Alexander Suvorov, Joan Bladé, Olga Samoylova, Thomas A Puchalski, Manjula Reddy, Rajesh Bandekar, Helgi van de Velde, Hong Xie, Jean-Franςois Rossi
• Journal: American journal of hematology (Am J Hematol) Vol. 90 Issue 1 Pg. 42-9 (Jan 2015) ISSN: 1096-8652 [Electronic] United States
• PMID: 25294016 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Antibodies, Monoclonal
• Boronic Acids
• IL6 protein, human
• Interleukin-6
• Pyrazines
• Bortezomib
• siltuximab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Boronic Acids (administration & dosage, adverse effects, therapeutic use)
• Bortezomib
• Disease-Free Survival
• Double-Blind Method
• Female
• Humans
• Interleukin-6 (immunology)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, immunology, mortality)
• Pyrazines (administration & dosage, adverse effects, therapeutic use)
• Recurrence