Hospital Universitario de Salamanca, Instituto de Biología Molecular y Celular del Cáncer, Universidad de Salamanca-Consejo Superior de Investigaciones Científicas, Salamanca, Spain.
N Engl J Med. 2013 Aug 1;369(5):438-47. doi: 10.1056/NEJMoa1300439.
For patients with smoldering multiple myeloma, the standard of care is observation until symptoms develop. However, this approach does not identify high-risk patients who may benefit from early intervention.
In this randomized, open-label, phase 3 trial, we randomly assigned 119 patients with high-risk smoldering myeloma to treatment or observation. Patients in the treatment group received an induction regimen (lenalidomide at a dose of 25 mg per day on days 1 to 21, plus dexamethasone at a dose of 20 mg per day on days 1 to 4 and days 12 to 15, at 4-week intervals for nine cycles), followed by a maintenance regimen (lenalidomide at a dose of 10 mg per day on days 1 to 21 of each 28-day cycle for 2 years). The primary end point was time to progression to symptomatic disease. Secondary end points were response rate, overall survival, and safety.
After a median follow-up of 40 months, the median time to progression was significantly longer in the treatment group than in the observation group (median not reached vs. 21 months; hazard ratio for progression, 0.18; 95% confidence interval [CI], 0.09 to 0.32; P<0.001). The 3-year survival rate was also higher in the treatment group (94% vs. 80%; hazard ratio for death, 0.31; 95% CI, 0.10 to 0.91; P=0.03). A partial response or better was achieved in 79% of patients in the treatment group after the induction phase and in 90% during the maintenance phase. Toxic effects were mainly grade 2 or lower.
Early treatment for patients with high-risk smoldering myeloma delays progression to active disease and increases overall survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00480363.).
对于冒烟型多发性骨髓瘤患者，标准治疗方案是观察，直到出现症状。然而，这种方法无法识别可能受益于早期干预的高危患者。
在这项随机、开放标签、3 期临床试验中，我们将 119 例高危冒烟型骨髓瘤患者随机分配至治疗组或观察组。治疗组患者接受诱导治疗方案（来那度胺，每天 25mg，第 1 至 21 天；地塞米松，每天 20mg，第 1 至 4 天及第 12 至 15 天；每 4 周为一个周期，共 9 个周期），随后接受维持治疗方案（来那度胺，每天 10mg，每 28 天周期的第 1 至 21 天，共 2 年）。主要终点是进展为有症状疾病的时间。次要终点是缓解率、总生存率和安全性。
中位随访 40 个月后，治疗组进展时间明显长于观察组（中位未达到 vs. 21 个月；进展风险比，0.18；95%置信区间 [CI]，0.09 至 0.32；P<0.001）。治疗组 3 年生存率也更高（94% vs. 80%；死亡风险比，0.31；95%CI，0.10 至 0.91；P=0.03）。治疗组患者在诱导阶段后有 79%达到部分缓解或更好，在维持阶段有 90%达到部分缓解或更好。毒性反应主要为 2 级或更低。
高危冒烟型骨髓瘤患者的早期治疗可延迟疾病进展为活动性疾病，并提高总生存率。（由 Celgene 资助；ClinicalTrials.gov 编号，NCT00480363。）
