TY - JOUR
T1 - Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma
AU - San-Miguel, Jesús
AU - Bladé, Joan
AU - Shpilberg, Ofer
AU - Grosicki, Sebastian
AU - Maloisel, Frédéric
AU - Min, Chang Ki
AU - Zarzuela, Marta Polo
AU - Robak, Tadeusz
AU - Prasad, Sripada V.S.S.
AU - Goh, Yeow Tee
AU - Laubach, Jacob
AU - Spencer, Andrew
AU - Mateos, María Victoria
AU - Palumbo, Antonio
AU - Puchalski, Tom
AU - Reddy, Manjula
AU - Uhlar, Clarissa
AU - Qin, Xiang
AU - Van De Velde, Helgi
AU - Xie, Hong
AU - Orlowski, Robert Z.
PY - 2014/6/26
Y1 - 2014/6/26
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84903642514
U2 - 10.1182/blood-2013-12-546374
DO - 10.1182/blood-2013-12-546374
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C2 - 24833354
AN - SCOPUS:84903642514
SN - 0006-4971
VL - 123
SP - 4136
EP - 4142
JO - Blood
JF - Blood
IS - 26
ER -