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

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/m 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.

BAFF and BAFF-Receptor in B Cell Selection and Survival

“…A second anti-BAFF antibody (tabalumab or LY2127399) has been tested in phase III studies and had similar effects like belimumab with an increase in complement activity and a decrease of anti-dsDNA IgG titers and B cell numbers leading to a mild clinical improvement in about 35% of patients treated in response to high dose treatment ( 114 ). The combination of tabalumab and bortezomib in a phase II study with multiple myeloma patients did not improve progression-free survival of the patients indicating that BAFF plays little or no role in disease progression ( 115 ). Similar to SLE, hyperactivated B cells are also discussed to play an important pathological role in the Sjögren's syndrome ( 116 ).…”

BAFF is involved in macrophage-induced bortezomib resistance in myeloma

“…It also enhances the survival of various B lymphocyte malignancies, including MM. 12 , 13 , 14 It can act as a membrane-bound or proteolytically cleaved soluble form displaying typical features of type II transmembrane protein. 15 It is expressed predominantly by stromal compartment including osteoclast, MΦs, dendritic cells, and some T cells.…”

Immunotherapy in Multiple Myeloma

“…Currently, it is being tested in patients with high-risk smoldering myeloma. Other antibodies being tested include anti-B-cell maturation antigen (BCMA) and tabalumab, a human anti-B-cell activating factor antibody [82]. The monoclonal antibodies are listed in Table 1.…”