Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Orlowski, R.Z.
Gercheva, L.
Williams, C.
Sutherland, H.
Robak, T.
Masszi, T.
Goranova-Marinova, V.
Dimopoulos, M.A.
Cavenagh, J.D.
Špička, I.
Maiolino, A.
Suvorov, A.
Bladé, J.
Samoylova, O.
Puchalski, T.A.
Reddy, M.
Bandekar, R.
van de Velde, H.
Xie, H.
Rossi, J.-F.
Περιοδικό:
American Journal of Hematology
Εκδότης:
Wiley-Liss, Inc.
Λέξεις-κλειδιά:
alanine aminotransferase; aspartate aminotransferase; bortezomib; C reactive protein; colony stimulating factor; dexamethasone; hemoglobin; interleukin 6; lenalidomide; placebo; siltuximab; triacylglycerol; antineoplastic agent; boronic acid derivative; bortezomib; IL6 protein, human; interleukin 6; monoclonal antibody; pyrazine derivative; siltuximab, adult; aged; alanine aminotransferase blood level; anemia; Article; aspartate aminotransferase blood level; bleeding; blood transfusion; bronchitis; cancer combination chemotherapy; cancer growth; cancer patient; cancer recurrence; cancer survival; constipation; controlled study; corticosteroid therapy; decreased appetite; diarrhea; double blind procedure; drug efficacy; drug megadose; drug safety; drug withdrawal; fatigue; febrile neutropenia; female; follow up; hemoglobin blood level; human; hypercholesterolemia; hypertriglyceridemia; major clinical study; male; maximum plasma concentration; multiple cycle treatment; multiple myeloma; neuralgia; neutropenia; overall survival; phase 2 clinical trial; pneumonia; priority journal; progression free survival; protein blood level; randomized controlled trial; rhinopharyngitis; salvage therapy; sensory neuropathy; thrombocytopenia; treatment duration; treatment response; triacylglycerol blood level; upper respiratory tract infection; clinical trial; disease free survival; immunology; Kaplan Meier method; middle aged; mortality; multiple myeloma; recurrent disease; very elderly, Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Disease-Free Survival; Double-Blind Method; Female; Humans; Interleukin-6; Kaplan-Meier Estimate; Male; Middle Aged; Multiple Myeloma; Pyrazines; Recurrence
