Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma
Journal
British Journal of Haematology
Journal Volume
176
Journal Issue
5
Pages
783-795
Date Issued
2017
Author(s)
Raje N.S.
Moreau P.
Terpos E.
Benboubker L.
Grząśko N.
Holstein S.A.
Oriol A.
Beksac M.
Kuliczkowski K.
Tai D.F.
Wooldridge J.E.
Conti I.
Kaiser C.J.
Nguyen T.S.
Cronier D.M.
Palumbo A.
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/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.
Subjects
B-cell activating factor (BAFF); bortezomib; multiple myeloma; tabalumab; treatment
SDGs
Other Subjects
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
Publisher
Blackwell Publishing Ltd
Type
journal article