Child J Anthony, Morgan Gareth J, Davies Faith E, Owen Roger G, Bell Susan E, Hawkins Kim, Brown Julia, Drayson Mark T, Selby Peter J
Academic Unit of Haematology and Oncology, Cancer Research United Kingdom Clinical Centre, University of Leeds, Leeds, United Kingdom.
N Engl J Med. 2003 May 8;348(19):1875-83. doi: 10.1056/NEJMoa022340.
High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer. In multiple myeloma, first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments, but evidence that this translates into improved survival is limited.
In this multicenter study, the Medical Research Council Myeloma VII Trial, we randomly assigned 407 patients with previously untreated multiple myeloma who were younger than 65 years of age to receive either standard conventional-dose combination chemotherapy or high-dose therapy and an autologous stem-cell transplant.
Among the 401 patients who could be evaluated, the rates of complete response were higher in the intensive-therapy group than in the standard-therapy group (44 percent vs. 8 percent, P<0.001). The rates of partial response were similar (42 percent and 40 percent, respectively; P=0.72), and the rates of minimal response were lower in the intensive-therapy group than in the standard-therapy group (3 percent vs. 18 percent, P<0.001). Intention-to-treat analysis showed a higher rate of overall survival (P=0.04 by the log-rank test) and progression-free survival (P<0.001) in the intensive-therapy group than in the standard-therapy group. As compared with standard therapy, intensive treatment increased median survival by almost 1 year (54.1 months [95 percent confidence interval, 44.9 to 65.2] vs. 42.3 months [95 percent confidence interval, 33.1 to 51.6]). There was a trend toward a greater survival benefit in the group of patients with a poor prognosis, as defined by a high beta2-microglobulin level (more than 8 mg per liter).
High-dose therapy with autologous stem-cell rescue is an effective first-line treatment for patients with multiple myeloma who are younger than 65 years of age.
高剂量疗法辅以自体干细胞移植仍是一种存在争议的癌症治疗方法。在多发性骨髓瘤中，包含高剂量疗法的一线治疗方案比传统剂量治疗产生更高的缓解率，但这种疗法能转化为生存期改善的证据有限。
在这项多中心研究——医学研究委员会骨髓瘤VII试验中，我们将407例年龄小于65岁且先前未经治疗的多发性骨髓瘤患者随机分配，分别接受标准传统剂量联合化疗或高剂量疗法及自体干细胞移植。
在401例可评估的患者中，强化治疗组的完全缓解率高于标准治疗组（分别为44%和8%；P<0.001）。部分缓解率相似（分别为42%和40%；P=0.72），强化治疗组的最小缓解率低于标准治疗组（3%对18%，P<0.001）。意向性分析显示，强化治疗组的总生存期（对数秩检验P=0.04）和无进展生存期（P<0.001）高于标准治疗组。与标准治疗相比，强化治疗使中位生存期延长近1年（54.1个月[95%置信区间为44.9至65.2]对42.3个月[95%置信区间为33.1至51.6]）。在β2微球蛋白水平高（超过8mg/L）定义的预后不良患者组中，有生存获益更大的趋势。
自体干细胞救援的高剂量疗法是65岁以下多发性骨髓瘤患者有效的一线治疗方法。
