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 ?pi?ka Angelo Maiolino Alexander Suvorov Joan Bladé Olga Samoylova Thomas A Puchalski Manjula Reddy Rajesh Bandekar Helgi van de Velde Hong Xie Jean‐Fran?ois Rossi |
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| Institution: | 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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