美法仑、泼尼松联合沙利度胺与单纯美法仑和泼尼松或减低强度自体干细胞移植治疗老年多发性骨髓瘤患者的疗效比较（IFM 99 - 06）：一项随机试验

Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial.

作者信息

Facon Thierry, Mary Jean Yves, Hulin Cyrille, Benboubker Lotfi, Attal Michel, Pegourie Brigitte, Renaud Marc, Harousseau Jean Luc, Guillerm Gaëlle, Chaleteix Carine, Dib Mamoun, Voillat Laurent, Maisonneuve Hervé, Troncy Jacques, Dorvaux Véronique, Monconduit Mathieu, Martin Claude, Casassus Philippe, Jaubert Jérôme, Jardel Henry, Doyen Chantal, Kolb Brigitte, Anglaret Bruno, Grosbois Bernard, Yakoub-Agha Ibrahim, Mathiot Claire, Avet-Loiseau Hervé

机构信息

Service d'Hématologie, Centre Hospitalier Universitaire, Lille, France.

出版信息

Lancet. 2007 Oct 6;370(9594):1209-18. doi: 10.1016/S0140-6736(07)61537-2.

DOI:10.1016/S0140-6736(07)61537-2

PMID:17920916

Abstract

BACKGROUND

In multiple myeloma, combination chemotherapy with melphalan plus prednisone is still regarded as the standard of care in elderly patients. We assessed whether the addition of thalidomide to this combination, or reduced-intensity stem cell transplantation, would improve survival.

METHODS

Between May 22, 2000, and Aug 8, 2005, 447 previously untreated patients with multiple myeloma, who were aged between 65 and 75 years, were randomly assigned to receive either melphalan and prednisone (MP; n=196), melphalan and prednisone plus thalidomide (MPT; n=125), or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 (MEL100; n=126). The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00367185.

FINDINGS

After a median follow-up of 51.5 months (IQR 34.4-63.2), median overall survival times were 33.2 months (13.8-54.8) for MP, 51.6 months (26.6-not reached) for MPT, and 38.3 months (13.0-61.6) for MEL100. The MPT regimen was associated with a significantly better overall survival than was the MP regimen (hazard ratio 0.59, 95% CI 0.46-0.81, p=0.0006) or MEL100 regimen (0.69, 0.49-0.96, p=0.027). No difference was seen for MEL100 versus MP (0.86, 0.65-1.15, p=0.32).

INTERPRETATION

The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should, at present, be the reference treatment for previously untreated elderly patients with multiple myeloma.

摘要

背景

在多发性骨髓瘤中，美法仑联合泼尼松的联合化疗仍被视为老年患者的标准治疗方案。我们评估了在该联合方案中添加沙利度胺或降低强度的干细胞移植是否能提高生存率。

方法

在2000年5月22日至2005年8月8日期间，447例年龄在65至75岁之间、先前未接受过治疗的多发性骨髓瘤患者被随机分配接受美法仑和泼尼松（MP；n = 196）、美法仑和泼尼松加沙利度胺（MPT；n = 125）或使用100 mg/m²美法仑进行降低强度的干细胞移植（MEL100；n = 126）。主要终点是总生存期。分析采用意向性治疗。该试验已在ClinicalTrials.gov注册，编号为NCT00367185。

结果

中位随访51.5个月（四分位间距34.4 - 63.2）后，MP组的中位总生存期为33.2个月（13.8 - 54.8），MPT组为51.6个月（26.6 - 未达到），MEL100组为38.3个月（13.0 - 61.6）。MPT方案与MP方案相比，总生存期显著更好（风险比0.59，95%可信区间0.46 - 0.81，p = 0.0006），与MEL100方案相比也是如此（0.69，0.49 - 0.96，p = 0.027）。MEL100与MP之间未观察到差异（0.86，0.65 - 1.15，p = 0.32）。