STRATEGIES FOR CURE IN NEWLY DIAGNOSED MULTIPLE MYELOMA

描述：(申请者描述)项目1将探索小说 新诊断多发性骨髓瘤患者的治疗策略 根据“全面治疗计划”取得的临床结果，开发和 在过去的供资期间建立的。全面治疗，包括 多方案诱导和清髓治疗在串联移植中的应用 环境，使骨髓瘤治疗最终取得进展，实现了 40%-50%的患者出现CRS，中位持续时间为50个月。这个 未来治疗的目标必须是进一步提高发病率和持续时间。 这是项目1的重点。我们将开发和测试新的 治疗策略基于我们长期的假设，即治疗 增加CR的发生率是获得更长无事件生存的关键 以及新诊断的骨髓瘤患者的总存活率。四个具体目标 将解决两个问题领域：能够实现高发病率 持续的CR和确定维持CR的障碍(基因定义 耐药性、肿瘤负担)。SA1：在随机的III期临床中进行评估 试验，是否将抗血管生成化合物沙利度胺添加到 综合治疗方案可提高缓解率，延长缓解期 作为新诊断患者的无事件和总存活率。SA2： 在随机试验中确定是否进一步强化 串联自体移植后的巩固治疗可提高CR率和 防止疾病复发。SA3：前瞻性地剖析基因 骨髓瘤的中期和间期FISH异质性研究 在治疗干预期间以规定的间隔进行核型分析 与提出的两个治疗试验问题有关的临床结果背景 在目标1和目标2中，SA4：系统地、前瞻性地评价， 轴位磁共振序列成像分析的应用价值 骨髓以记录骨髓受累的模式和程度(肿瘤负担) 以及治疗期间的变化(“MR-CR”)，因为它们与结果有关。这些研究 是对上一次资助期间获得的结果的合乎逻辑的延伸 与在其他5个项目中进行的研究和与 访问3个核心，将提供目前无法获得的对骨髓瘤的见解 生物学和舞台表演。

DESCRIPTION: (Applicant's Description) Project 1 will explore novel therapeutic strategies for newly diagnosed MM patients in an effort to improve upon clinical results obtained with the "Total Therapy Program," developed and instituted during the past funding period. Total Therapy, which comprises multi-regimen induction and myeloablative therapy in the tandem transplant setting, has allowed advances in myeloma therapy to be made at last, achieving CRs in 40-50 percent of patients, which lasted a median of 50 months. The goal of future therapies must be to further enhance the incidence and duration of CR, which is the focus of Project 1. We will develop and test new treatment strategies based on our long-standing hypothesis that therapies that increase the incidence of CR are key to eliciting longer event-free survival and overall survival in newly diagnosed myeloma patients. Four specific aims will address two problem areas: being able to achieve a high incidence of sustained CR and identifying obstacles to sustaining CR (genetically defined resistance, tumor burden). SA1: Evaluate, in a randomized phase III clinical trial, whether the addition of the anti-angiogenesis compound, thalidomide, to the total therapy regimen can improve CR rate and extend CR duration as well as event-free and overall survival in newly diagnosed patients. SA2: Determine, in a randomized trial, whether further intensification of consolidation therapy after tandem autotransplants can increase CR rate and prevent disease recurrence. SA3: Prospectively dissect the genetic heterogeneity of myeloma by performing metaphase and interphase FISH karyotyping at defined intervals during therapeutic intervention in the context of clinical outcome related to the 2 therapeutic trial questions posed in Aims 1 & 2. SA4: Evaluate, systematically and in a prospective fashion, the usefulness of serial magnetic resonance (MR) imaging analysis of axial marrow to document the pattern and extent of marrow involvement (tumor burden) and changes during therapy ("MR-CR") as they relate to outcome. These studies are a logical extension of the findings obtained during the previous funding period and, in concert with research conducted in 5 other projects and with access to 3 cores, will provide currently unavailable insights into myeloma biology and staging.