title: Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma.
abstract: In this double-blind, Phase 2 study, 220 patients with relapsed/refractory multiple myeloma were randomly assigned 1:1:1 to receive placebo (N = 72), tabalumab 100 mg (N = 74), or tabalumab 300 mg (N = 74), each in combination with dexamethasone 20 mg and subcutaneous bortezomib 1·3 mg/m2on a 21-day cycle. No significant intergroup differences were observed among primary (median progression-free survival [mPFS]) or secondary efficacy outcomes. The mPFS was 6·6, 7·5 and 7·6 months for the tabalumab 100, 300 mg and placebo groups, respectively (tabalumab 100 mg vs. placebo Hazard ratio (HR) [95% confidence interval (CI)] = 1·13 [0·80-1·59], P = 0·480; tabalumab 300 mg vs. placebo HR [95% CI] = 1·03 [0·72-1·45], P = 0·884). The most commonly-reported treatment-emergent adverse events were thrombocytopenia (37%), fatigue (37%), diarrhoea (35%) and constipation (32%). Across treatments, patients with low baseline BAFF (also termed TNFSF13B) expression (n = 162) had significantly longer mPFS than those with high BAFF expression (n = 55), using the 75th percentile cut-off point (mPFS [95% CI] = 8·3 [7·0-9·3] months vs. 5·8 [3·7-6·6] months; HR [95% CI] = 1·59 [1·11-2·29], P = 0·015). Although generally well tolerated, PFS was not improved during treatment with tabalumab compared to placebo. A higher dose of 300 mg tabalumab did not improve efficacy compared to the 100 mg dose. Nonetheless, BAFF appears to have some prognostic value in patients with multiple myeloma.
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Noopur S
authors.initials: NS
authors.lastname: Raje
authors.affiliation: University Hospital Hôtel-Dieu, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.affiliation: Hôpital Bretonneau, Centre Hospitalier Régional Universitaire (CHRU), Tours, France.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benboubker
authors.affiliation: Medical University of Lublin and Department of Haematology, St. John's Cancer Centre, Lublin, Poland.
authors.forename: Norbert
authors.initials: N
authors.lastname: Grząśko
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Holstein
authors.affiliation: Institut Català d'Oncologia (ICO) and Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: National Taiwan University, Medical College and Hospital, Taipei, Taiwan.
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Ankara University Ibn Sina Hospital, Ankara, Turkey.
authors.forename: Meral
authors.initials: M
authors.lastname: Beksac
authors.affiliation: Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Datchen F
authors.initials: DF
authors.lastname: Tai
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Wooldridge
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Conti
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kaiser
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Tuan S
authors.initials: TS
authors.lastname: Nguyen
authors.affiliation: Eli Lilly and Company Limited, Windlesham, Surrey, UK.
authors.forename: Damien M
authors.initials: DM
authors.lastname: Cronier
authors.affiliation: Myeloma Unit, Division of Haematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069286:Bortezomib; D003907:Dexamethasone; C575974:tabalumab
keywords: B-cell activating factor (BAFF); bortezomib; multiple myeloma; tabalumab; treatment