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 |
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| Authors: | 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‐Franςois Rossi |
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| Affiliation: | 1. Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas;2. University Hospital for Active Treatment “St. Marina,”, Varna, Bulgaria;3. Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom;4. Vancouver General Hospital, Vancouver, Canada;5. Medical University of ?ód? and Copernicus Memorial Hospital, ?ód?, Poland;6. St. Istvan and St. Laszlo Hospital of Budapest and Semmelweis University, Budapest, Hungary;7. University Multiprofile Hospital for Active Treatment “St. George,”, Plovdiv, Bulgaria;8. National and Kapodistrian University of Athens, Athens, Greece;9. St. Bartholomew's and the London Hospital, London, United Kingdom;10. Charles University in Prague, Prague, Czech Republic;11. Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;12. First Republican Clinical Hospital of Udmurtia, Izhevsk, Russia;13. Hospital Clinic i Provincial and Institut d'Investigacions Biomediques August Pi I Sunyer, Barcelona, Spain;14. Nizhniy Novgorod Region Clinical Hospital, Nizniy Novgorod, Russia;15. Janssen Research & Development, Spring House, Pennsylvania;16. Janssen Research & Development, Beerse, Belgium;17. University Hospital CHU Saint Eloi and INSERM U1040, Montpellier, France |
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| 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. © 2014 Wiley Periodicals, Inc. Am. J. Hematol. 90:42–49, 2015. © 2014 Wiley Periodicals, Inc. |
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