Maintenance Treatment with Thalidomide after Autologous Transplantation for Myeloma: Final Analysis of a Prospective Randomized Study of the “Intergroupe Francophone du Myelome”.

Author:

Attal Michel1,Harousseau Jean-Luc1,Leyvraz Serge1,Doyen Chantal1,Hulin Cyrille1,Benboubker Lofti1,Agha Ibrahim Yakoub1,Bourhis Jean-Henri1,Garderet Laurent1,Sotto Jean-Jacques1,Michallet Mauricette1,Renaud Marc1,Voillat Laurent1,Berthou Christian1,Marit Gerald1,Monconduit Mathieu1,Dumonté Charles1,Caillot Denis1,Mathiot Claire1,Avet-Loiseau Hervé1,

Affiliation:

1. Service d’Hématologie, Hôpital Purpan, Toulouse, France

Abstract

Abstract High dose therapy (HDT) supported with autologous stem cell transplantation has been introduced in the management of myeloma. However, after a single or a double transplantation, almost all patients ultimately relapse. New strategies are required to control the residual disease after HDT. The “Intergroupe Françophone du Myélome” (IFM) initiated a trial designed to evaluate the impact of maintenance treatment with Thalidomide on the duration of response after HDT. From April 2000 to October 2003, 1017 myeloma patients at diagnosis under the age of 65 years were enrolled in the IFM 99 protocol. 780 of them, without or with only one adverse prognostic factor (beta-2 microglobuline ≥ 3 mg/l or deletion of chromosome 13), were enrolled in the IFM 99 02 protocol. They received the following treatment: 1) 3–4 cycles of the VAD regimen; 2) a first autologous transplant prepared with Melphalan 140 mg/m2; 3) a second autologous transplant prepared with Melphalan 200 mg/m2. Patients without progressive disease 2 months after the second transplant were randomized to receive: no maintenance treatment (arm A), maintenance treatment with Pamidronate (arm B) or maintenance treatment with Thalidomide and Pamidronate (arm C). As of June 2005, 593 patients (76%) have been randomized: 197 in arm A, 195 in arm B and 201 in arm C. Clinical characteristics of each group were similar. The median follow-up from diagnosis was 3 years (1 to 6 y). Thalidomide was found to improve the Event-free-survival (EFS). Indeed, the 4-year post-diagnosis probability of EFS was 39% (95% CI= 29–51) in arm A, 37% (95% CI= 26–48) in arm B, and 50% (95% CI= 37–60) in arm C (p<0.02). We compared EFS according to the treatment groups in different subgroups of patients (beta-2-microglobulin ≤ 2.5 mg/l, beta-2-microglobulin > 2.5 mg/l, deletion of chromosome 13, and no deletion of chromosome 13). Thalidomide was found to improve the 4-year EFS of patients without deletion of chromosome 13 (39% in arm A, 38% in arm B, 52% in arm C, p<0.01) and of patients with a beta-2-microglobulin > 2.5 mg/l at diagnosis (28% in arm A, 21% in arm B, 57% in arm C, p<0.001). On the opposite, patients with a deletion of chromosome 13 or with a beta-2-microglobulin ≤ 2.5 mg/l at diagnosis did not benefit significantly from Thalidomide (p=0.5 and p=0.9, respectively). The 4-year overall survival was similar in the 3 treatment groups: 86% in arm A, 78% in arm B, and 86% in arm C (NS). Among the 593 randomized patients, 3 factors were found to be associated with a longer EFS in the multivariate analysis: low beta-2-microglobulin at diagnosis (p<0.03), treatment arm (p<0.02), and deletion of chromosome 13 (p<0.03). In conclusion, the final analysis of the IFM9902 trial demonstrates that Thalidomide improves the duration of response after high dose therapy among patients with myeloma, especially those who have a beta-2-microglobulin >2.5 mg/l without deletion of chromosome 13.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Cited by 11 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3