Total Therapy 3 for multiple myeloma: prognostic implications of cumulative dosing and premature discontinuation of VTD maintenance components, bortezomib, thalidomide, and dexamethasone, relevant to all phases of therapy
Total Therapy 3 for multiple myeloma: prognostic implications of cumulative dosing and premature discontinuation of VTD maintenance components, bortezomib, thalidomide, and dexamethasone, relevant to all phases of therapy
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DOI：
10.1182/blood-2010-01-264333
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发表时间：
2010-08-26
期刊：
影响因子：
20.3
通讯作者：
Barlogie, Bart
中科院分区：
文献类型：
--
作者：
van Rhee, Frits;Szymonifka, Jackie;Barlogie, Bart
采用时间相关的方法，研究了硼替佐米(V)、沙利度胺(T)和地塞米松(D)的累积剂量和过早停药（PMDD）对总治疗3的总生存期（OS）、无事件生存期（EFS）、到下一次治疗的时间和复发后生存期的影响，这些影响与诱导期、移植期、巩固期和维持期相关。在诱导、巩固（除T）和维持（除V和T）期间，所有药物均使用较高剂量，则OS和EFS更长。D诱导剂量对OS和EFS的有利影响为检测糖皮质激素受体NR3C1的表达提供了理论依据，高水平的糖皮质激素受体NR3C1显著延长OS和EFS，并使结果与D和T剂量无关，而在低水平的NR3C1环境中，T和D（而不是V）剂量对结果改善至关重要。V组的PMDD是OS的一个独立的高度不良特征（风险比= 6.44;P < 0.001），而T和D组的PMDD分别缩短了下一次治疗的时间。任何VTD成分的剂量对复发后生存没有不良影响，并且确实从V中获益，这支持了所有活性药物以剂量密集和剂量强化的方式预先使用，正如总治疗3所实践的那样，以最大化骨髓瘤生存。[血液，2010;116(8):1220-1227]
The impact of cumulative dosing and premature drug discontinuation (PMDD) of bortezomib (V), thalidomide (T), and dexamethasone (D) on overall survival (OS), event-free survival (EFS), time to next therapy, and post-relapse survival in Total Therapy 3 were examined, using time-dependent methodology, relevant to induction, peritransplantation, consolidation, and maintenance phases. Univariately, OS and EFS were longer in case higher doses were used of all agents during induction, consolidation (except T), and maintenance (except V and T). The favorable OS and EFS impact of D induction dosing provided the rationale for examining the expression of glucocorticoid receptor NR3C1, top-tertile levels of which significantly prolonged OS and EFS and rendered outcomes independent of D and T dosing, whereas T and D, but not V, dosing was critical to outcome improvement in the bottom-tertile NR3C1 setting. PMDD of V was an independent highly adverse feature for OS (hazard ratio = 6.44; P < .001), whereas PMDD of both T and D independently imparted shorter time to next therapy. The absence of adverse effects on postrelapse survival of dosing of any VTD components and indeed a benefit from V supports the use up-front of all active agents in a dose-dense and dose-intense fashion, as practiced in Total Therapy 3, toward maximizing myeloma survival. (Blood. 2010; 116(8): 1220-1227)