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

Noopur S. Raje, Philippe Moreau, Evangelos Terpos, Lotfi Benboubker, Norbert Grząśko, Sarah A. Holstein, Albert Oriol, Shang Yi Huang, Meral Beksac, Kazimierz Kuliczkowski, Datchen F. Tai, James E. Wooldridge, Ilaria Conti, Christopher J. Kaiser, Tuan S. Nguyen, Damien M. Cronier, Antonio Palumbo

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13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)783-795
Number of pages13
JournalBritish Journal of Haematology
Volume176
Issue number5
DOIs
Publication statusPublished - Mar 1 2017

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Keywords

  • B-cell activating factor (BAFF)
  • bortezomib
  • multiple myeloma
  • tabalumab
  • treatment

ASJC Scopus subject areas

  • Hematology

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