Comparative modeling of multiple myeloma across myeloma control continuuum: prevention, treatment, and disparity reduction

项目摘要/摘要 多发性骨髓瘤(MM)是一种常见的致命性血液系统恶性肿瘤。多发性骨髓瘤的治疗进展迅速 不断进化。虽然这些新疗法显著提高了存活率，但中位存活率仍在43-43之间。 确诊时83个月。在所有癌症站点中，MM的管理成本最高，这在一定程度上可以 归因于指南建议的多种药物方案。尽管如此重要的健康和经济 多发性骨髓瘤治疗的负担和快速变化的格局，多发性骨髓瘤不是癌症中的癌症部位之一 干预和监督建模网络(CISNET)。因此，MM缺乏可供设置的比较模型 MM预防和控制的目标和政策优先顺序。此外，与乳腺癌或结直肠癌不同 癌症，目前还没有针对MM的基于人群的筛查，也没有针对患有MM的患者的风险管理策略 癌前状态(MGUS和阴燃MM)。MM需要比较建模来评估 前景看好的干预策略，特别是在癌前阶段。防止/控制这种毁灭性的 在防治艾滋病方面，必须在实施之前证明这些干预措施的潜力。此外， 多发性骨髓瘤的显著种族差异(发病率和存活率)由来已久。没有任何基于价值的 在预防和治疗策略方面，MM健康差距将继续恶化。这个孵化器项目 将包括两个建模小组在协调下进行对比建模 中间。我们的计划将评估预防或治疗多发性骨髓瘤的新策略，目标是减少 MM的负担和缓解MM的差距。我们计划对比建立、校准和验证证据- 基于跨MM护理连续体的MM建模(目标1)。利用所提出的比较模型，我们 将(1)评估新的MM预防策略对诊断为MGUS的高危患者的影响(AIM 2)；(2)评估新治疗方案和指南推荐方案的成本-效果 诊断为多发性骨髓瘤患者的治疗(目标3)；以及(3)评估在什么情况下和在 通过拟议的新干预措施，可以通过哪些方式实现消除种族差距的目标 战略(目标4)。拟议的MM孵化器计划的重要意义在于它有能力1)建立证据- 基于MM的比较建模，相对于实体区域而言，疾病区域缺少此类建模 已建立此类模型的肿瘤，以指导干预和政策；2)提供循证评估 在实施任何昂贵的临床试验之前；3)探索不同阶段的新干预措施/治疗方法 4)检查指南推荐的疗法的价值，提供证据以告知 指南，从而改变了目前MGUS和MM治疗的临床实践。建议数 对MGUS和MM患者的干预策略是创新的，目标是预防和控制MM 并缩小MM的差距。这项研究的成功完成将在有形指标上提供证据，以敦促 从目前的MGUS/MM管理模式转变。因此，这是推动这一领域向前迈出的关键一步。

PROJECT SUMMARY/ABSTRACT Multiple myeloma (MM) is a common and lethal hematologic malignancy. Treatments of MM have been rapidly evolving. While these new treatments improve survival considerably, the median survival still ranges from 43- 83 months at diagnosis. Among all cancer sites, the management of MM is the most costly, which in part can be attributable to guideline recommended multidrug regimens. Despite such significant health and economic burdens and rapid changing landscape for MM treatments, MM is not one of the cancer sites in the Cancer Intervention and Surveillance Modeling Network (CISNET). Therefore, MM lacks comparative modeling to set goals and policy prioritization in MM prevention and control. Moreover, unlike breast cancer or colorectal cancer, there exists no population-based screening for MM or risk managed strategies for those with premalignant conditions (MGUS and smoldering MM). MM requires comparative modeling to evaluate promising intervention strategies, particularly at premalignant stages. To prevent/control this devastating disease, it is imperative to demonstrate the potentials of these interventions before implementation. Moreover, marked racial disparities in MM (both incidence and survival) is long-established. Without any value-based strategies for prevention and treatment, MM health disparities will continue to worsen. This Incubator Program will include two modeling groups to conduct comparative modeling under the coordination of the coordinating center. Our Program will evaluate novel strategies in preventing or treating MM with the goals of reducing the burden of MM and mitigating MM disparities. We plan to comparatively build, calibrate, and validate evidence- based MM modeling across the MM care continuum (Aim 1). Using the proposed comparatively modeling, we will (1) assess the impacts of novel MM prevention strategies in high-risk patients diagnosed with MGUS (Aim 2); (2) evaluate the cost-effectiveness of novel treatment regimens as well as guideline-recommended treatments in patients diagnosed with MM (Aim 3); and (3) assess whether, under what conditions, and in which ways the goal of eliminating racial disparities can be achieved through the proposed novel intervention strategies (Aim 4). The proposed MM Incubator Program is significant in its capability to 1) build evidence- based comparative modeling for MM, a disease area that lacks of such modeling, relative to the areas of solid tumors already with such modeling, to guide interventions and policies; 2) provide evidence-based evaluation before implementation of any costly clinical trial; 3) explore novel interventions/treatments at various stages of MM; and 4) examine the value of guideline-recommended therapies, providing evidence to inform changes in guidelines and thus a shift in current clinical practice of MGUS and MM management. The proposed intervention strategies for MGUS and MM patients are innovative, with the goals to prevent and control MM and reduce MM disparities. Successful completion of this study will provide evidence in tangible metrics to urge a paradigm shift from current MGUS/MM management. It is therefore a vital step to move the field forward.