TY - JOUR
TI - Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma
AU - Raje, N.S.
AU - Moreau, P.
AU - Terpos, E.
AU - Benboubker, L.
AU - Grząśko, N.
AU - Holstein, S.A.
AU - Oriol, A.
AU - Huang, S.-Y.
AU - Beksac, M.
AU - Kuliczkowski, K.
AU - Tai, D.F.
AU - Wooldridge, J.E.
AU - Conti, I.
AU - Kaiser, C.J.
AU - Nguyen, T.S.
AU - Cronier, D.M.
AU - Palumbo, A.
JO - British Journal of Haematology
PY - 2017
VL - 176
TODO - 5
SP - 783-795
PB - Wiley-Blackwell Publishing Ltd
SN - 0007-1048, 1365-2141
TODO - 10.1111/bjh.14483
TODO - bortezomib;  dexamethasone;  placebo;  tabalumab;  antineoplastic agent;  bortezomib;  dexamethasone;  monoclonal antibody;  tabalumab, adult;  aged;  anemia;  area under the curve;  Article;  cancer combination chemotherapy;  constipation;  controlled study;  coughing;  diarrhea;  dizziness;  double blind procedure;  drug efficacy;  drug safety;  drug tolerability;  drug withdrawal;  fatigue;  febrile neutropenia;  female;  human;  insomnia;  kidney failure;  major clinical study;  male;  maximum plasma concentration;  multicenter study;  multiple cycle treatment;  multiple myeloma;  nausea;  overall survival;  peripheral edema;  peripheral neuropathy;  phase 2 clinical trial;  pneumonia;  progression free survival;  randomized controlled trial;  sensory neuropathy;  sepsis;  septic shock;  thrombocytopenia;  time to maximum plasma concentration;  upper respiratory tract infection;  clinical trial;  complication;  disease free survival;  middle aged;  mortality;  multiple myeloma;  procedures;  salvage therapy;  treatment outcome, Adult;  Aged;  Antibodies, Monoclonal;  Antineoplastic Combined Chemotherapy Protocols;  Bortezomib;  Dexamethasone;  Disease-Free Survival;  Double-Blind Method;  Female;  Humans;  Male;  Middle Aged;  Multiple Myeloma;  Salvage Therapy;  Treatment Outcome
TODO - 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/m2 on 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. � 2016 John Wiley & Sons Ltd
ER -