TY - JOUR
T1 - 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, Noopur S.
AU - Moreau, Philippe
AU - Terpos, Evangelos
AU - Benboubker, Lotfi
AU - Grząśko, Norbert
AU - Holstein, Sarah A.
AU - Oriol, Albert
AU - Huang, Shang Yi
AU - Beksac, Meral
AU - Kuliczkowski, Kazimierz
AU - Tai, Datchen F.
AU - Wooldridge, James E.
AU - Conti, Ilaria
AU - Kaiser, Christopher J.
AU - Nguyen, Tuan S.
AU - Cronier, Damien M.
AU - Palumbo, Antonio
N1 - Publisher Copyright:
© 2016 John Wiley & Sons Ltd
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - B-cell activating factor (BAFF)
KW - bortezomib
KW - multiple myeloma
KW - tabalumab
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=85007137226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85007137226&partnerID=8YFLogxK
U2 - 10.1111/bjh.14483
DO - 10.1111/bjh.14483
M3 - Article
C2 - 28005265
AN - SCOPUS:85007137226
SN - 0007-1048
VL - 176
SP - 783
EP - 795
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 5
ER -