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
Massachusetts General Hospital, Boston, MA, USA.
University Hospital Hôtel-Dieu, Nantes, France.
Br J Haematol. 2017 Mar;176(5):783-795. doi: 10.1111/bjh.14483. Epub 2016 Dec 22.
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.
在这项双盲2期研究中，220例复发/难治性多发性骨髓瘤患者按1:1:1随机分组，分别接受安慰剂（N = 72）、100 mg塔巴单抗（N = 74）或300 mg塔巴单抗（N = 74）治疗，每种药物均与20 mg地塞米松及皮下注射硼替佐米1.3 mg/m²联合使用，每21天为一个周期。在主要疗效指标（中位无进展生存期[mPFS]）或次要疗效指标方面，未观察到显著的组间差异。塔巴单抗100 mg组、300 mg组和安慰剂组的mPFS分别为6.6个月、7.5个月和7.6个月（塔巴单抗100 mg组与安慰剂组相比，风险比[HR][95%置信区间（CI）]=1.13[0.80 - 1.59]，P = 0.480；塔巴单抗300 mg组与安慰剂组相比，HR[95%CI]=1.03[0.72 - 1.45]，P = 0.884）。最常报告的治疗中出现的不良事件为血小板减少（37%）、疲劳（37%）、腹泻（35%）和便秘（32%）。在所有治疗组中，以第75百分位数为界点，基线BAFF（也称为TNFSF13B）表达低的患者（n = 162）的mPFS显著长于BAFF表达高的患者（n = 55）（mPFS[95%CI]=8.3[7.0 - 9.3]个月对5.8[3.7 - 6.6]个月；HR[95%CI]=1.59[1.11 - 2.29]，P = 0.015）。尽管塔巴单抗一般耐受性良好，但与安慰剂相比，治疗期间PFS并未改善。与100 mg剂量相比，300 mg更高剂量的塔巴单抗并未提高疗效。尽管如此，BAFF似乎在多发性骨髓瘤患者中具有一定的预后价值。
