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

作者：Orlowski Robert Z^*; Gercheva Liana; Williams Cathy; Sutherland Heather; Robak Tadeusz; Masszi Tamas; Goranova Marinova Vesselina; Dimopoulos Meletios A; Cavenagh James D; Spicka Ivan; Maiolino Angelo; Suvorov Alexander; Blade Joan; Samoylova Olga; Puchalski Thomas A; Reddy Manjula; Bandekar Rajesh; van de Velde Helgi; Xie Hong; Rossi Jean Francois

来源：American Journal of Hematology, 2015, 90(1): 42-49.

DOI：10.1002/ajh.23868

We compared the safety and efficacy of siltuximab (S), an anti-interleukin-6 chimeric monoclonal antibody, plus bortezomib (B) with placebo (plc) 1 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 1 B and plc 1 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 1 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 1 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.

• 出版日期2015-1