Division of Hematology-Oncology, Mayo Clinic in Arizona, 13400 East Shea Blvd, Scottsdale, AZ 85259, USA.
Blood. 2013 Feb 28;121(9):1517-23. doi: 10.1182/blood-2012-09-451872. Epub 2013 Jan 7.
We conducted a randomized, controlled trial comparing thalidomide-prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m2. The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival,progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide-prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio = 0.77; P = .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio = 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P = .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomide-prednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit.
我们进行了一项随机对照试验,比较了沙利度胺-泼尼松作为维持治疗与观察在 332 例接受马法兰 200mg/m2 自体干细胞移植的患者中的疗效。主要终点是总生存期(OS);次要终点是骨髓瘤特异性无进展生存期、无进展生存期、静脉血栓栓塞发生率和健康相关生活质量(HRQoL)。中位随访 4.1 年后,未发现沙利度胺-泼尼松与观察之间的 OS 存在差异(分别为 4 年估计值为 68%和 60%;风险比=0.77;P=0.18);沙利度胺-泼尼松与更好的骨髓瘤特异性无进展生存期和无进展生存期相关(两种结果的 4 年估计值分别为 32%和 14%;风险比=0.56;P<0.0001),并且静脉血栓栓塞发生率更高(7.3%与无;P=0.0004)。沙利度胺-泼尼松组首次疾病复发后的中位生存期为 27.7 个月,观察组为 34.1 个月。沙利度胺-泼尼松组观察到 9 例二次恶性肿瘤,观察组为 6 例。分配至沙利度胺-泼尼松组的患者在认知功能、呼吸困难、便秘、口渴、腿部肿胀、麻木、口干和平衡问题等方面的 HRQoL 较差。我们的结论是,自体干细胞移植后用沙利度胺-泼尼松维持治疗可延长疾病控制时间,但与患者报告的 HRQoL 恶化有关,并且未检测到 OS 获益。