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研究者在法国报告指出，将thalidomide加入含melphalan和prednisone(MP)的标准治疗中，可以改善新诊断之年长多发性骨髓瘤（multiple myeloma）病患的无恶化和整体存活。Melphalan和prednisone用于不适合高剂量治疗之年长病患的标准治疗，但是根据一篇发表于10月6日Lancet期刊中的新研究，thalidomide必须加入MP处方中。
研究者认为melphalan/prednisone/thalidomide(MPT) 目前必须变成新诊断多发性骨髓瘤之年长病患的参考治疗方式。
在一篇伴随而来的编辑评论中，义大利Torino大学的Antonio Palumbo医师表示，经过50年来不断尝试发现新的更有效的治疗方式之后，我们现在有了大规模证据支持引用MPT作为多发性骨髓瘤年长病患的标准照护。
他们指出，潜在治疗利益必须与不良反应的风险平衡；此案例中，MPT的血栓栓塞以及周边神经病变风险比MP高，但我们认为我们已经知道如何处理这些不良反应。
主要研究者，法国Lille大学医学中心的Thierry Facon医师和同事评估将thalidomide加入标准的MP是否可以减低强度干细胞移植而对存活有正面影响。
研究者表示，已知Thalidomide对复发或者难治多发性骨髓瘤有实际的抗肿瘤活性，但是对新诊断病患的效果尚不清楚；当并用melphalan和prednisone或者合并进入高剂量治疗，thalidomide会增加反应率，包括完整反应以及提高无意外存活率，但是增加了毒性反应以及缺乏有关整体存活的显著效果。
在2000年5月到2005年4月之间，447位年纪在65到75岁新诊断第II或第III期多发性骨髓瘤病患被随积分到以下3组治疗：标准MP、MPT或者使用melphalan 100 mg/m2 (MEL100)的减低强度干细胞移植；适合高剂量治疗的65岁以下病患也被纳入试验中，所有治疗组同时接受每天1040 mg的clodronate。
平均追踪36.8个月，使用MPT处方的病患有最好的整体存活；接受MEL100 和 MP的病患，其整体存活相似；51.5个月时，研究者观察发现，使用MPT处方的病患，其平均整体存活是51.6个月，MP组是 33.2个月，MEL100 组是38.3个月。
他们也指出，接受MPT的病患比较不会出现早期和毒性死亡，治疗最初3个月的死亡率在MP组为7%，在MPT组为2%，在MEL100组为9%；不过，MPT组比MP组有较高的嗜中性白血球过低症，接受thalidomide的病患有12%发生栓塞或者肺栓塞；等级3或以上的非血液毒性反应在MP组最低；MEL100组出现较频繁的严重感染和心脏毒性反应。
研究者指出，虽然MPT组的毒性反应比MP组高， 但是早期和毒性死亡发生率比较低。
他们表示，其试验结果提供有力证据支持并用MPT，因此，目前可以作为之前未治疗之年长多发性骨髓瘤病患的参考治疗。
作者中有3位接受来自Pharmion, Janssen Cilag以及Celgene的科学谘商会议与演讲费用，该研究获得Lille大学医学中心的赞助，研究资金来自法国健康部，以及瑞士的临床癌症研究小组。
Thalidomide Improves Survival for Older Patients With Multiple Myeloma
By Roxanne Nelson
Medscape Medical News
The addition of thalidomide to standard treatment with melphalan and prednisone (MP) can improve progression-free and overall survival in newly diagnosed elderly multiple myeloma patients, researchers in France report. Melphalan and prednisone have been the standard treatment for elderly patients who are ineligible for high-dose therapy, but according to the results of a new study published in the October 6, 2007 issue of the Lancet, thalidomide should be added to the MP regimen.
The researchers suggest that melphalan/prednisone/thalidomide (MPT) should become, as least for the present time, the reference treatment for elderly patients newly diagnosed with multiple myeloma.
In an accompanying editorial, Antonio Palumbo, MD, and Mario Boccadoro, MD, from the University of Torino, in Italy, write, "After 50 years of unsuccessful attempts to find new and more effective treatment approaches suitable for most patients, we now have extensive evidence to support the introduction of MPT as the standard of care for elderly patients with multiple myeloma."
They do point out that potential benefits always need to be balanced against increased risks for adverse events. In this case, MPT is associated with a higher risk for thromboembolism and peripheral neuropathy, compared with MP, but "we should also consider that we have learned how to manage these adverse events," they note.
Lead investigator Thierry Facon, MD, from the Centre Hospitalier Universitaire, in Lille, France, and colleagues assessed whether the addition of thalidomide to the standard MP combination or to reduced-intensity stem-cell transplantation might positively influence survival.
Thalidomide has shown substantial antitumor activity in patients with relapsed or refractory multiple myeloma, but in newly diagnosed patients, its usefulness is yet unclear, write the researchers. "When used in combination with melphalan and prednisone or incorporated into high-dose treatment, thalidomide has increased response rates, including complete response, and has extended the event-free survival but increases toxic effects and lacks a significant effect on overall survival."
During the period from May 2000 to April 2005, 447 patients between the ages of 65 and 75 years who were newly diagnosed with stage II or III multiple myeloma were randomized to 1 of 3 treatment groups: standard MP, MPT, or reduced-intensity stem-cell transplantation using melphalan 100 mg/m2 (MEL100). Patients younger than 65 years were also included in the trial if deemed ineligible for high-dose treatment, and all treatment groups also received clodronate, at a dose of 1040 mg per day.
At a median follow-up of 36.8 months, patients on the MPT regimen had better overall survival, as compared with those in the 2 other treatment groups. Patients receiving MEL100 and MP had similar rates of overall survival. At 51.5 months, the researchers observed that the median overall survival for patients receiving MPT was 51.6 months, compared with 33.2 months for MP and 38.3 months for MEL100.
They also noted that early and toxic deaths appeared to occur less frequently in patients who received MPT. Mortality rates during the first 3 months of treatment were 7% in the MP group, 2% in the MPT group, and 9% in MEL100 group. However, there was a higher rate of neutropenia among patients receiving MPT, as compared with MP, and 12% of patients who received thalidomide experienced thrombosis or pulmonary embolism. Nonhematologic toxic effects of grade 3 or more were lower in the MP group as compared with MPT or MEL100; severe infections and cardiac toxic effects were observed more frequently in patients receiving MEL100.
Even though the toxic effects associated with MPT were higher than those observed in patients receiving MP, they were counterbalanced by a low incidence of toxic and early deaths, note the researchers.
"The results of our trial provide strong evidence to suggest that the MPT combination, should, at present, be the reference treatment for previously untreated elderly patients with multiple myeloma," they write.
Three of the authors have received scientific adviser board and lecture fees from Pharmion, Janssen Cilag, and Celgene. The study was supported by the Centre Hospitalier et Universitaire de Lille, by a research grant from the French Ministry of Health, and by the Swiss Group for Clinical Cancer Research.
Lancet. 2007;370:1209-1218.