Garban Frederic, Attal Michel, Michallet Mauricette, Hulin Cyrille, Bourhis Jean H, Yakoub-Agha Ibrahim, Lamy Thierry, Marit Gerald, Maloisel Frederic, Berthou Christian, Dib Mamoun, Caillot Denis, Deprijck Bernard, Ketterer Nicolas, Harousseau Jean-Luc, Sotto Jean-Jacques, Moreau Philippe
Hematology Department, University Hospital Hôtel-Dieu, Place Ricordeau, 44093 Nantes cedex 01, France.
Blood. 2006 May 1;107(9):3474-80. doi: 10.1182/blood-2005-09-3869. Epub 2006 Jan 5.
The Intergroupe Francophone du Myélome (IFM) initiated 2 trials in 1999 to study patients with high-risk (beta2-microglobulin level greater than 3 mg/L and chromosome 13 deletion at diagnosis) de novo multiple myeloma. In both protocols, the induction regimen consisted of vincristine, doxorubicin, and dexamethasone (VAD) followed by first autologous stem cell transplantation (ASCT) prepared by melphalan 200 mg/m(2). Patients with an HLA-identical sibling donor were subsequently treated with dose-reduced allogeneic stem cell transplantation (IFM99-03 trial), and patients without an HLA-identical sibling donor were randomly assigned to undergo second ASCT prepared by melphalan 220 mg/m(2) and 160 mg dexamethasone with or without anti-IL-6 monoclonal antibody (IFM99-04 protocol). Two hundred eighty-four patients-65 in the IFM99-03 trial and 219 in the IFM99-04 trial-were prospectively treated and received at least one course of VAD. On an intent-to-treat basis, overall survival (OS) and event-free survival (EFS) did not differ significantly in the studies (medians 35 and 25 months in the IFM99-03 trial vs 41 and 30 months in the IFM99-04 trial, respectively). With a median follow-up time of 24 months, the EFS of the 166 patients randomly assigned in the tandem ASCT protocol was similar to the EFS of the 46 patients who underwent the entire IFM99-03 program (median, 35 vs 31.7 months), with a trend for a better OS in patients treated with tandem ASCT (median, 47.2 vs 35 months; P = .07). In patients with high-risk de novo MM, the combination of ASCT followed by dose-reduced allogeneic transplantation was not superior to tandem dose-intensified, melphalan-based ASCT.
法语骨髓瘤研究组（IFM）于1999年启动了2项试验，以研究高危（β2-微球蛋白水平大于3 mg/L且诊断时存在13号染色体缺失）初发多发性骨髓瘤患者。在这两个方案中，诱导方案均为由长春新碱、阿霉素和地塞米松（VAD）组成，随后进行首次自体干细胞移植（ASCT），移植前使用美法仑200 mg/m²预处理。有 HLA 相合同胞供者的患者随后接受剂量降低的异基因干细胞移植（IFM99-03试验），而没有 HLA 相合同胞供者的患者则被随机分配接受第二次ASCT，移植前使用美法仑220 mg/m²和160 mg地塞米松，加或不加抗IL-6单克隆抗体（IFM99-04方案）。284例患者——IFM99-03试验中的65例和IFM99-04试验中的219例——接受了前瞻性治疗并接受了至少一个疗程的VAD。在意向性治疗的基础上，两项研究中的总生存期（OS）和无事件生存期（EFS）没有显著差异（IFM99-03试验的中位数分别为35个月和25个月，IFM99-04试验的中位数分别为41个月和30个月）。中位随访时间为24个月时，串联ASCT方案中随机分配的166例患者的EFS与接受整个IFM99-03方案的46例患者的EFS相似（中位数分别为35个月和31.7个月），串联ASCT治疗的患者OS有改善趋势（中位数分别为47.2个月和35个月；P = 0.07）。在高危初发MM患者中，ASCT后进行剂量降低的异基因移植的联合方案并不优于串联剂量强化的基于美法仑的ASCT。
