Phase 2 study of tabalumab, a human anti‐B‐cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma

• Published in: British journal of haematology Vol. 176; no. 5; pp. 783 - 795
• Main Authors: Raje, Noopur S., Moreau, Philippe, Terpos, Evangelos, Benboubker, Lotfi, Grząśko, Norbert, Holstein, Sarah A., Oriol, Albert, Huang, Shang‐Yi, Beksac, Meral, Kuliczkowski, Kazimierz, Tai, Datchen F., Wooldridge, James E., Conti, Ilaria, Kaiser, Christopher J., Nguyen, Tuan S., Cronier, Damien M., Palumbo, Antonio
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.03.2017
• Subjects: Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BLyS protein; Bortezomib; Bortezomib - administration & dosage; B‐cell activating factor (BAFF); Constipation; Dexamethasone; Dexamethasone - administration & dosage; Diarrhea; Disease-Free Survival; Double-Blind Method; Fatigue; Female; Hematology; Humans; Lymphocytes B; Male; Middle Aged; Multiple myeloma; Multiple Myeloma - complications; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Salvage Therapy - methods; tabalumab; Thrombocytopenia; treatment; Treatment Outcome; B-cell activating factor (BAFF); treatment; multiple myeloma; bortezomib; tabalumab
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.14483

Summary 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.