Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma.
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 ≥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.gov as #NCT00911859.
Centro de Investigación Medica Aplicada, Clinica Universidad de Navarra, Navarra, Spain;
Jesús
J
San-Miguel
Institut d'Investigacions Biomediques August Pi I Sunyer, Hospital Clinic I Provincial, Barcelona, Spain;
Joan
J
Bladé
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel;
Ofer
O
Shpilberg
Oddzial Hematologiczny SPZOZ Zespol Szpitali Miejskich w Chorzowie, Chorzow, Poland;
Sebastian
S
Grosicki
Clinique Saint Anne, Strasbourg, France;
Frédéric
F
Maloisel
Seoul St. Mary's Hospital, Seoul, Republic of Korea;
Chang-Ki
CK
Min
Hospital Clinico San Carlos, Madrid, Spain;
Marta
M
Polo Zarzuela
Medical University of Lodz, Lodz, Poland;
Tadeusz
T
Robak
Apollo Hospitals & Research Foundation, Hyderabad, India;
Sripada V S S
SV
Prasad
Singapore General Hospital, Singapore, Singapore;
Yeow
Y
Tee Goh
Dana Farber Cancer Institute, Boston, MA;
Jacob
J
Laubach
Alfred Health-Monash University, Melbourne, Australia;
Andrew
A
Spencer
Hospital Universitario Salamanca, Salamanca, Spain;
María-Victoria
MV
Mateos
Ospedale Le Molinette, Torino, Italy;
Antonio
A
Palumbo
Janssen Research & Development, Spring House, PA;
Tom
T
Puchalski
Janssen Research & Development, Spring House, PA;
Manjula
M
Reddy
Janssen Research & Development, Spring House, PA;
Clarissa
C
Uhlar
Janssen Research & Development, Spring House, PA;
Xiang
X
Qin
Janssen Research & Development, Beerse, Belgium; and.
Helgi
H
van de Velde
Janssen Research & Development, Spring House, PA;
Hong
H
Xie
The University of Texas MD Anderson Cancer Center, Houston, TX.
Robert Z
RZ
Orlowski
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D015996:Survival Rate; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
D000911:Antibodies, Monoclonal; D001897:Boronic Acids; D000069286:Bortezomib; D007070:Immunoglobulin A; D008558:Melphalan; D011241:Prednisone; D011719:Pyrazines; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; D015850:Interleukin-6; C504234:siltuximab