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达雷木单抗、来那度胺和地塞米松治疗多发性骨髓瘤的研究
Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma


Meletios A. Dimopoulos ... 肿瘤 • 2016.10.06
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达雷木单抗联合来那度胺、地塞米松治疗复发难治多发性骨髓瘤疗效显著


陆佩华

陆道培医院,国际淋巴瘤骨髓瘤中心

 

多发性骨髓瘤是常见的血液恶性肿瘤之一。多年来科学家、临床医师们前赴后继致力于提高此病患者的生存率。随着对此疾病发病机制的深入探讨研究,治疗此病的新药尤其是靶向药层出不穷。此病的治疗效果明显得到改善。仅2015年11月美国FDA就批准了3种新药应用于治疗难治复发的骨髓瘤,这其中就包括达雷木单抗。

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摘要


背景

在复发或难治性多发性骨髓瘤的一期与二期试验中,无论是单独治疗还是与来那度胺及地塞米松联合治疗,达雷木单抗均显示出良好的疗效。

 

方法

在本项三期试验中,我们将569例此前曾经接受过一线或多线治疗的多发性骨髓瘤患者随机分组,接受来那度胺与地塞米松单独治疗(对照组),或接受来那度胺、地塞米松与达雷木单抗联合治疗(达雷木单抗组)。主要终点是无进展生存期。

 

结果

在研究方案规定的中期分析中,在中位随访时间为13.5个月时,作者观察到169例疾病进展或死亡事件(286例达雷木单抗组患者中出现53例[18.5%],而283例对照组中出现116例[41.0%];风险比为0.37;95%可信区间[CI]为0.27~0.52;分层时序检验P<0.001)。Kaplan–Meier分析结果显示,达雷木单抗组12个月的无进展生存率为83.2%(95% CI,78.3%~87.2%),而对照组为60.1%(95% CI,54.0%~65.7%)。我们观察到,达雷木单抗组总体缓解率显著高于对照组(92.9%对76.4%,P<0.001),达雷木单抗组中完全缓解或疗效较好的患者比例也较高(43.1%对19.2%,P<0.001)。在达雷木单抗组中,22.4%的患者肿瘤细胞数量低于微小残留病的阈值(每105个白细胞中有1个肿瘤细胞),而对照组则为4.6%(P<0.001);肿瘤细胞数量低于微小残留病阈值与结局改善相关。治疗过程中最常见的3级或4级不良事件包括中性粒细胞减少(达雷木单抗组为51.9%,而对照组为37.0%)、血小板减少(12.7%对13.5%)和贫血(12.4%对19.6%)。47.7%的患者发生达雷木单抗引起的输液相关反应,并且多为1级或2级反应。

 

结论      

在来那度胺与地塞米松基础上联合应用达雷木单抗,显著延长了复发或难治性多发性骨髓瘤患者的无进展生存期。达雷木单抗与输液相关的反应和中性粒细胞减少的发生率高于对照组(本项研究由Janssen Research and Development资助;POLLUX在ClinicalTrials.gov注册号为NCT02076009)。





作者信息

Meletios A. Dimopoulos, M.D., Albert Oriol, M.D., Hareth Nahi, M.D., Jesus San-Miguel, M.D., Nizar J. Bahlis, M.D., Saad Z. Usmani, M.D., Neil Rabin, M.B., B.S., Ph.D., Robert Z. Orlowski, M.D., Mieczyslaw Komarnicki, M.D., Kenshi Suzuki, M.D., Torben Plesner, M.D., Sung-Soo Yoon, M.D., Dina Ben Yehuda, M.D., Paul G. Richardson, M.D., Hartmut Goldschmidt, M.D., Donna Reece, M.D., Steen Lisby, M.D., Nushmia Z. Khokhar, M.D., Lisa O’Rourke, M.S.N., Christopher Chiu, Ph.D., Xiang Qin, M.S., Mary Guckert, M.S.N., Tahamtan Ahmadi, M.D., and Philippe Moreau, M.D., for the POLLUX Investigators*
Address reprint requests to Dr. Dimopoulos at the National and Kapodistrian University of Athens, School of Medicine, Alexandra Hospital, 80 Vas. Sofias, Athens 11528, Greece, or at mdimop@med.uoa.gr. *A complete list of investigators in the POLLUX trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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