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Siltuximab was given by 6 mg\/kg IV every 2 weeks. On progression, B was discontinued and high\u2010dose dexamethasone could be added to S\/plc. Response and progression\u2010free survival (PFS) were analyzed pre\u2010dexamethasone 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, <jats:italic>P<\/jats:italic> = 0.345), overall response rate was 55 versus 47% (<jats:italic>P<\/jats:italic> = 0.213), complete response rate was 11 versus 7%, and median overall survival (OS) was 30.8 versus 36.8 months (HR 1.353, <jats:italic>P<\/jats:italic> = 0.103). Sustained suppression of C\u2010reactive protein, a marker reflective of inhibition of interleukin\u20106 activity, was seen with S + B. Siltuximab did not affect B pharmacokinetics. Siltuximab\/placebo discontinuation (75 versus 66%), grade \u22653 neutropenia (49 versus 29%), thrombocytopenia (48 versus 34%), and all\u2010grade 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. \u00a9 2014 Wiley Periodicals, Inc. Am. J. 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