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

作者：San Miguel Jesus^*; Blade Joan; Shpilberg Ofer; Grosicki Sebastian; Maloisel Frederic; Min Chang Ki; Polo Zarzuela Marta; Robak Tadeusz; Prasad Sripada V S S; Goh Yeow Tee; Laubach Jacob; Spencer Andrew; Mateos Maria Victoria; Palumbo Antonio; Puchalski Tom; Reddy Manjula; Uhlar Clarissa; Qin Xiang; van de Velde Helgi; Xie Hong; Orlowski Robert Z

来源：Blood, 2014, 123(26): 4136-4142.

DOI：10.1182/blood-2013-12-546374

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 =.0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the 2 arms. Grade %26gt;= 3 adverse-event incidence was 92% on S+VMP and 81% on VMP (P =.09), with trends toward more hematologic events and infections on S+VMP. Maintenance therapy with siltuximab was well tolerated. In conclusion, the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes. This study was registered at http://clinicaltrials.govas # NCT00911859.

• 出版日期2014-6-26