Curing myeloma at last: defining criteria and providing the evidence
Curing myeloma at last: defining criteria and providing the evidence
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DOI：
10.1182/blood-2014-07-552059
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发表时间：
2014-11-13
期刊：
影响因子：
20.3
通讯作者：
Crowley, John
中科院分区：
文献类型：
--
作者：
Barlogie, Bart;Mitchell, Alan;Crowley, John
多发性骨髓瘤不治之症的教条还成立吗？骨髓瘤的基因组混乱和由此产生的对细胞凋亡的抵抗，长期以来被认为是治愈的障碍，形成了全面治疗（TT）计划的基础。TT方法在初始治疗期间预先使用所有骨髓瘤活性药物靶向耐药亚克隆，以防止以后复发。1202例患者的长期随访（TT1: n=231，中位随访：21年；TT2: 668，中位随访：12年；TT3a: n=303，中位随访：9年）允许调查无进展生存（PFS）和完全缓解（CR）持续时间是否与可治愈性一致，即观察PFS和CR持续时间在Kaplan-Meier图中的平台。在627例具有浆细胞基因表达谱数据的患者亚组中，14%的高风险骨髓瘤患者在5年出现明显的治愈平台期，而其余低风险骨髓瘤患者在10年出现明显的治愈平台期。基于PFS和CR持续时间的参数模型支持治愈率的增加：10年PFS和CR估计从TT1的8.8%/17.9%增加到TT2对照组的15.5%/28.2%，TT2沙利度胺组的25.1%/35.6%和TT3a的32.9%/48.8%。为了开发新的治疗方法，我们建议将重点放在预后尚未进展的高危骨髓瘤患者身上。
Does the dogma that multiple myeloma is incurable still hold?. The genomic chaos and resulting resistance to apoptosis of myeloma, long considered an obstacle to cure, formed the basis of Total Therapy (TT) program. The TT approach uses all myelomaactive drugs upfront to target drug-resistant subclones during initial treatment to prevent later relapse. Long-term follow-up of 1202 patients (TT1: n=231, median follow-up: 21 years; TT2: 668, median follow-up: 12 years; TT3a: n=303, median follow-up: 9 years) permitted investigation of whether progression-free survival (PFS) and complete response (CR) duration were consistent with curability, ie observation of plateaus in Kaplan-Meier plots for PFS and CR duration. In the subset of 627 patients with plasma cell gene expression profiling data, cure plateaus were apparent at 5 years in the 14% with high-risk myeloma compared with 10 years in the remainder with low-risk disease. A parametric model based on PFS and CR duration supported an increase in curability: 10-year PFS and CR estimates increased from 8.8%/17.9% in TT1 to 15.5%/28.2% in TT2's control arm to 25.1%/35.6% in TT2's thalidomide arm and to 32.9%/48.8% in TT3a. Toward developing novel therapies, we recommend a concerted focus on patients with high-risk myeloma whose outcome has not been advanced.