新诊断多发性骨髓瘤患者的持续治疗与固定疗程治疗的比较。
Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma.
机构信息
Antonio Palumbo, Francesca Gay, Federica Cavallo, Alessandra Larocca, Francesca Donato, Chiara Cerrato, Luana Boccadifuoco, and Mario Boccadoro, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino; Giulia Benevolo, S.C. Ematologia A.O. Città della Salute e della Scienza di Torino; Tommasina Guglielmelli, University of Turin and San Luigi Hospital; Giovannino Ciccone, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino and CPO Piemonte, Torino; Francesco Di Raimondo, Ospedale Ferrarotto, Azienda Policlinico-OVE, University of Catania, Catania; Maria T. Petrucci, Sapienza University of Rome; Tommaso Caravita, Ematologia Ospedale S. Eugenio, Rome; Sara Pezzatti, Azienda Ospedaliera San Gerardo, Monza; Francesca Patriarca, DISM, University Hospital, Udine; Chiara Nozzoli, AOU Careggi, Florence; Donatella Vincelli, A.O "Bianchi-Melacrino-Morelli," Reggio Calabria; Pellegrino Musto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Referral Cancer Center of Basilicata, Rionero in Vulture; Paolo Corradini, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milano, Milano; Michele Cavo, Institute of Hematology and Medical Oncology "Seràgnoli," Bologna University School of Medicine S. Orsola's University Hospital, Bologna, Italy; Izhar Hardan, Meir Medical Center, Kfar-Saba; Arnon Nagler, Tel Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel; Roman Hajek, University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic; Michel Delforge, University Hospital Leuven, Leuven, Belgium; Zhinuan Yu and Christian Jacques, Celgene, Summit, NJ; and Meletios A. Dimopoulos, National and Kapodistrian University of Athens, School of Medicine, Alexandra Hospital, Athens, Greece.
出版信息
J Clin Oncol. 2015 Oct 20;33(30):3459-66. doi: 10.1200/JCO.2014.60.2466. Epub 2015 Aug 17.
PURPOSE
Continuous therapy (CT) prolongs progression-free survival 1 (PFS1; time from random assignment until the first progression or death), but chemotherapy-resistant relapse may negatively impact overall survival (OS). Progression-free survival 2 (PFS2; time from random assignment until the second progression or death) may represent an additional tool to estimate outcome. This study evaluates the benefit of novel agent-based CT versus fixed duration of therapy (FDT) in patients with newly diagnosed myeloma.
METHODS
We included patients enrolled onto three phase III trials that randomly assigned patients to novel agent-based CT versus FDT. Primary analyses were restricted to the intent-to-treat population eligible for CT (patients progression free and alive at 1 year after random assignment). Primary end points were PFS1, PFS2, and OS. All hazard ratios (HRs) and 95% CIs were adjusted for several potential confounders using Cox models.
RESULTS
In the pooled analysis of the three trials, 604 patients were randomly assigned to CT and 614 were assigned to FDT. Median follow-up was 52 months. In the intent-to-treat CT population, CT (n = 417), compared with FDT (n = 410), significantly improved PFS1 (median, 32 v 16 months, respectively; HR, 0.47; 95% CI, 0.40 to 0.56; P < .001), PFS2 (median, 55 v 40 months, respectively; HR, 0.61; 95% CI, 0.50 to 0.75; P < .001), and OS (4-year OS, 69% v 60%, respectively; HR, 0.69; 95% CI, 0.54 to 0.88; P = .003).
CONCLUSION
In this pooled analysis, CT significantly improved PFS1, PFS2, and OS. The improvement in PFS2 suggests that the benefit reported during first remission is not cancelled by a shorter second remission. PFS2 is a valuable end point to estimate long-term clinical benefit and should be included in future trials.
目的
连续治疗（CT）可延长无进展生存期 1（PFS1；从随机分组到第一次进展或死亡的时间），但化疗耐药性复发可能会对总生存期（OS）产生负面影响。无进展生存期 2（PFS2；从随机分组到第二次进展或死亡的时间）可能是另一种评估结果的工具。本研究评估了新型药物为基础的 CT 与固定疗程治疗（FDT）在新诊断骨髓瘤患者中的疗效。
方法
我们纳入了三项随机分配患者接受新型药物为基础的 CT 或 FDT 的 III 期临床试验中的患者。主要分析仅限于有资格接受 CT（随机分组后 1 年仍无进展且存活的患者）的意向治疗人群。主要终点为 PFS1、PFS2 和 OS。使用 Cox 模型，对所有风险比（HR）和 95%置信区间（CI）进行了多种潜在混杂因素的调整。
结果
在这三项试验的汇总分析中，604 例患者被随机分配至 CT 组，614 例患者被分配至 FDT 组。中位随访时间为 52 个月。在意向治疗 CT 人群中，CT（n=417）与 FDT（n=410）相比，PFS1（中位，32 个月对 16 个月；HR，0.47；95%CI，0.40 至 0.56；P<0.001）、PFS2（中位，55 个月对 40 个月；HR，0.61；95%CI，0.50 至 0.75；P<0.001）和 OS（4 年 OS，69%对 60%；HR，0.69；95%CI，0.54 至 0.88；P=0.003）均显著改善。
结论
在本汇总分析中，CT 显著改善了 PFS1、PFS2 和 OS。PFS2 的改善提示，首次缓解期间报告的获益不会因第二次缓解期缩短而被抵消。PFS2 是评估长期临床获益的有价值的终点，应纳入未来的临床试验。
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