BACKGROUND Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved. METHODS In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring. Treatment was continued for 39 cycles, for 36 months, or until confirmation of disease progression, whichever occurred first. The primary end point was progression-free survival; progression to active multiple myeloma was assessed by an independent review committee in accordance with International Myeloma Working Group diagnostic criteria. RESULTS Among the 390 enrolled patients, 194 were assigned to the daratumumab group and 196 to the active-monitoring group. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.67; P<0.001). Progression-free survival at 5 years was 63.1% with daratumumab and 40.8% with active monitoring. A total of 15 patients (7.7%) in the daratumumab group and 26 patients (13.3%) in the active-monitoring group died (hazard ratio, 0.52; 95% CI, 0.27 to 0.98). Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was hypertension, which occurred in 5.7% and 4.6% of the patients in the daratumumab group and the active-monitoring group, respectively. Adverse events led to treatment discontinuation in 5.7% of the patients in the daratumumab group, and no new safety concerns were identified. CONCLUSIONS Among patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and with higher overall survival than active monitoring. No unexpected safety concerns were identified. (Funded by Janssen Research and Development; AQUILA ClinicalTrials.gov number, NCT03301220.).

中文翻译：

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Daratumumab 或高危冒烟多发性骨髓瘤的主动监测。


背景 Daratumumab 是一种抗 CD38 单克隆抗体，已被批准用于治疗多发性骨髓瘤。需要有关使用 daratumumab 治疗高危冒烟多发性骨髓瘤的数据，这是一种活动性多发性骨髓瘤的前体疾病，尚未批准治疗方法。方法 在这项 3 期试验中，我们将高危冒烟多发性骨髓瘤患者随机分配接受皮下注射 daratumumab 单药治疗或积极监测。治疗持续 39 个周期，持续 36 个月，或直到确认疾病进展，以先发生者为准。主要终点是无进展生存期;独立审查委员会根据国际骨髓瘤工作组诊断标准评估活动性多发性骨髓瘤的进展。结果 在 390 例入组患者中，194 例被分配到 daratumumab 组，196 例被分配到主动监测组。中位随访 65.2 个月，daratumumab 组疾病进展或死亡风险比主动监测组低 51%（风险比，0.49;95% 置信区间 [CI]，0.36 至 0.67;P<0.001）。daratumumab 组的 5 年无进展生存率为 63.1%，主动监测组为 40.8%。daratumumab 组共有 15 例患者 （7.7%） 和主动监测组 26 例患者 （13.3%） 死亡 （风险比，0.52;95% CI，0.27 至 0.98）。daratumumab 组 5 年总生存率为 93.0%，主动监测组为 86.9%。最常见的 3 级或 4 级不良事件是高血压，分别发生在 daratumumab 组和 active 监测组的 5.7% 和 4.6% 的患者中。不良事件导致 5 人停止治疗。daratumumab 组为 7% 的患者，未发现新的安全性问题。结论 在高危冒烟型多发性骨髓瘤患者中，皮下注射 daratumumab 单药治疗与进展为活动性多发性骨髓瘤或死亡的风险显著降低相关，并且总生存期高于主动监测。没有发现意外的安全问题。（由 Janssen Research and Development 资助;AQUILA ClinicalTrials.gov 号，NCT03301220.）。