A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma.
A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma.
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无症状（冒烟）多发性骨髓瘤 (AMM) 患者转化为活动性多发性骨髓瘤 (MM) 的风险很高。唑来膦酸 (ZLD) 等双膦酸盐可减少 MM 中的骨骼事件，而免疫调节剂沙利度胺 (Thal) 已被证明对活动性 MM 有效。我们假设，与单独使用 ZLD 相比，Thal 和 ZLD 治疗会延长 MM 进展时间 (TTP)。符合条件的患者为无症状 MM，所有患者每月接受 ZLD 4 mg 静脉注射；治疗组每天还接受 200 毫克 Thal 治疗。 Thal/ZLD (n = 35) 患者的 TTP 优于单独 ZLD (n = 33)；中位 TTP 为 2.4 年（95% 置信区间 (CI)：1.4–3.6）对比 1.2 年（95% CI：0.7–2.5）（风险比 (HR)，2.05；95% CI：1.1–3.8；P 值：0.02）。 1 年时，86% 的 Thal/ZLD 患者无进展，而仅使用 ZLD 的患者为 55%（P = 0.0048）。 Thal/ZLD 第 1 年后的总体缓解率为 37%，中位缓解持续时间为 3.3 年（95% CI：1.1-NA）；单独对 ZLD 没有确认的反应（P = 0.0004）。将 Thal 添加到标准 ZLD 中会产生抗肿瘤反应，而单独的 ZLD 不会产生抗肿瘤反应。 Thal/ZLD 还延长了从 AMM 到 MM 的 TTP。这项研究为进一步研究 AMM 患者延迟化疗提供了依据。
Patients with asymptomatic (smoldering) multiple myeloma (AMM) have a high risk of transformation to active multiple myeloma (MM). Bisphosphonates such as zoledronic acid (ZLD) reduce skeletal events in MM and the immunomodulatory agent thalidomide (Thal) has proven effectiveness in active MM. We hypothesized that treatment with Thal and ZLD would prolong the time to progression (TTP) to MM over ZLD alone. Eligible patients had asymptomatic MM and all patients received ZLD 4 mg intravenous monthly; the treatment arm also received Thal 200 mg per day. The TTP was superior for Thal/ZLD (n =35) patients compared with ZLD alone (n =33); median TTP of 2.4 years (95% confidence interval (CI): 1.4–3.6) versus 1.2 years (95% CI: 0.7–2.5) (hazard ratio (HR), 2.05; 95% CI: 1.1–3.8; P-value: 0.02). At 1 year, 86% of Thal/ZLD patients were progression free compared with 55% on ZLD alone (P =0.0048). The overall response rate after year 1 was 37% for Thal/ZLD with a median duration of response of 3.3 years (95% CI: 1.1-NA); there were no confirmed responses to ZLD alone (P =0.0004). The addition of Thal to standard ZLD produces anti-tumor responses whereas ZLD alone does not. Thal/ZLD also prolongs TTP from AMM to MM. This study provides the rationale for further studies in patients with AMM to delay chemotherapy.