Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma

Jesús San-Miguel, Joan Bladé, Ofer Shpilberg, Sebastian Grosicki, Frédéric Maloisel, Chang Ki Min, Marta Polo Zarzuela, Tadeusz Robak, Sripada V.S.S. Prasad, Yeow Tee Goh, Jacob Laubach, Andrew Spencer, María Victoria Mateos, Antonio Palumbo, Tom Puchalski, Manjula Reddy, Clarissa Uhlar, Xiang Qin, Helgi Van De Velde, Hong XieRobert Z. Orlowski

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

Because interleukin-6 (IL-6) is considered important in the proliferation of early multiple myeloma (MM), we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone (VMP) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM. One hundred and six patients were randomized to receive 9 cycles of VMP or VMP plus siltuximab (11 mg/kg every 3 weeks) followed by siltuximab maintenance. Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions. With a complete response (CR) rate of 27% on siltuximab plus VMP (S+VMP) and 22% on VMP, the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10%. Overall response rate was 88% on S+VMP and 80% on VMP, and at least very good partial response rates were 71% and 51% (P 5 .0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the 2 arms. Grade ≥3 adverse-event incidence was 92% on S1VMP and 81% on VMP ( P = .09), with trends toward more hematologic events and infections on S+VMP. Maintenance therapy with siltuximabwaswell tolerated. In conclusion, the addition of siltuximab toVMPdid not improve theCRrate or long-term outcomes. This study was registered at http://clinicaltrials.gov as #NCT00911859.

Original languageEnglish
Pages (from-to)4136-4142
Number of pages7
JournalBlood
Volume123
Issue number26
DOIs
StatePublished - 26 Jun 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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