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

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 Franois Rossi

Research output: Article

74 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalAmerican Journal of Hematology
Volume90
Issue number1
DOIs
Publication statusPublished - jan. 1 2015

ASJC Scopus subject areas

  • Hematology

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    Orlowski, R. Z., Gercheva, L., Williams, C., Sutherland, H., Robak, T., Masszi, T., Goranova-Marinova, V., Dimopoulos, M. A., Cavenagh, J. D., Špička, I., Maiolino, A., Suvorov, A., Bladé, J., Samoylova, O., Puchalski, T. A., Reddy, M., Bandekar, R., van de Velde, H., Xie, H., & Rossi, J. F. (2015). 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. American Journal of Hematology, 90(1), 42-49. https://doi.org/10.1002/ajh.23868