Tailored monitoring of patients with monoclonal gammopathy to improve early detection of myeloma and monoclonal gammopathy of clinical significance

对单克隆丙种球蛋白病患者进行定制监测，以提高骨髓瘤和单克隆丙种球蛋白病的早期发现，具有临床意义

• 批准号: MR/V037439/2
• 负责人: Karthik Ramasamy
• 金额: $ 12.48万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV037439%2F2
• 关键词: Tailored; monitoring; patients; monoclonal; gammopathy

Earlier detection is a high priority for patients and improves survival: 84% of people with myeloma survive for >5 years if diagnosed at the earliest stage, compared with only 26% if diagnosed at advanced stage. Myeloma is most frequently diagnosed late (>3-6 months post symptom presentation) and has the longest diagnostic delay of any cancer, with emergency presentations in >30% of newly diagnosed myeloma patients who have shortened survival, cancer arising from bone marrow, is the 20th most common cause of cancer deaths worldwide and remains incurable. Myeloma (MM) is often diagnosed at an advanced stage when it has multiple effects on patients' overall well-being, including bone disease, kidney disease, and a weakened immune system. Recent treatments have improved life expectancy and quality of life. The earlier that myeloma is diagnosed and treated, the more effectively symptoms are controlled, improving patient survival and reducing healthcare costs associated with treating late-stage myeloma and attendant co-morbidities. Every myeloma arises from a preceding, often symptomless and undiagnosed condition called Monoclonal Gammopathy of Undetermined Significance (MGUS), occurring in ~3% people aged 50 years and over. Screening >50s for MGUS and monitoring for progression using the existing inexpensive diagnostic blood test would enable myeloma early diagnosis but is unlikely to be cost-effective as most people with MGUS do not develop MM. Monoclonal gammopathy of clinical significance (MGCS) is a recently coined termed to capture a set of monoclonal gammopathy patients who have kidney impairment, nerve damage, bone fractures or skin lesions directly linked to the presence or deposition of the monoclonal protein. Lack of recognition of this clinical association leads to diagnostic delay and irreversible damage to organs involved. Therefore, we aim to specifically identify MGUS patients at high risk of progression to myeloma and / or MGCS. Objective 1: Understanding the symptom burden, and additional clinical parameters driving the test request, which lands an incidental diagnosis of MGUS is key. Using access to Clinical practice research data link (CPRD) primary care records on patients coded as monoclonal gammopathy to generate this dataset. We will identify set of predictors for transformation from MGUS to MM. CPRD data will also enable identification of clinical associations recently described as MGCS conditions. Objective 2: Oxford University Hospital, we have recently established the OxCom clinical service funded by Oxfordshire Clinical Commissioning Group to improve serial MGUS monitoring for patients in the Oxfordshire community. This funding has been allocated to address the lack of serial follow up of MGUS patients; patients are often lost to follow up, and GPs' are unable to address clinical concerns generated by MGUS patients in primary care. This OxCom infrastructure enables us to generate a prospective dataset with detailed clinical and laboratory data. Hypothesis generating observations generated from the CPRD datasets can be validate in this prospective MGUS database. We will validate the primary care prection model in the OxCom database. Objective 3: Recent observations have shown that aberrant changes to light chains secrete dby MGUS patients can help predict who would develop MGCS, and/or potentially transform to myeloma. Working with Department of Chemistry at Oxford we can prospectively evaluate these preliminary observations in the surplus patient samples obtained from the OxCom service. These shared research-enabling resources will help drive improvements in early diagnosis and MGUS/myeloma care in the NHS.My vision is to harness the multidisciplinary expertise in Oxford across big data analysis (primary care data), joined up secondary care clinical services and protein chemistry expertise to improve monitoring of MGUS patients, and enable early diagnosis of MGCS and myeloma.

早期检测是患者的高度优先级，并且可以提高生存率：如果在最早的阶段被诊断出，有84％的骨髓瘤患者的生存率超过5年，而如果在高级阶段被诊断出，则只有26％。骨髓瘤最常被诊断晚期（症状后3-6个月> 3-6个月），并且在任何癌症的诊断延迟中最长，紧急表现率在> 30％的新诊断的骨髓瘤患者中，这些患者缩短了生存率，癌症是由骨髓引起的，是全球癌症死亡的第20个最常见的原因，并且是全球范围内的癌症死亡原因。骨髓瘤（MM）经常在晚期诊断出对患者的整体健康状况的多种影响，包括骨骼疾病，肾脏疾病和免疫系统弱。最近的治疗方法改善了预期寿命和生活质量。骨髓瘤越早被诊断和治疗，控制症状越有效，改善了患者的生存率，并降低了与治疗后期骨髓瘤和伴随合并症有关的医疗保健费用。每个骨髓瘤都来自前一个未定义（mgus）的单克隆肾上腺病（MGU）的前一个，通常是无症状和未诊断的疾病，发生在约30岁及以上的3％的人中。使用现有廉价的诊断血液检查的筛查> 50s的MGU和监测进展，可以使骨髓瘤早期诊断，但由于大多数MGU患者不发展MM，因此不太可能具有成本效益。临床意义（MGC）的单克隆性伽马病（MGC）是一种被称为捕获一组单克隆性γ-患者，这些单克隆性γ-患者患有肾脏损伤，神经损伤，骨折或皮肤病变，直接与单克隆蛋白的存在或沉积有关。缺乏对这种临床关联的认识会导致诊断延迟和对涉及的器官的不可逆转损害。因此，我们旨在特别识别出高度进展为骨髓瘤和 /或MGC的MGUS患者。目的1：了解症状负担和推动测试请求的其他临床参数，该请求将偶然诊断为MGU是关键。使用访问临床实践研究数据链接（CPRD）的初级保健记录，以编码为单克隆性伽马病的患者生成该数据集。我们将确定从MGU到MM转换的一组预测指标。 CPRD数据还将鉴定最近描述为MGCS条件的临床关联。目标2：牛津大学医院，我们最近建立了由牛津郡临床调试小组资助的OXCOM临床服务，以改善牛津郡社区患者的连续MGU监测。这项资金已分配给MGUS患者缺乏连续的随访；患者通常会失去随访，而GPS无法解决MGUS患者在初级保健中产生的临床问题。该OXCOM基础设施使我们能够生成一个具有详细临床和实验室数据的预期数据集。在此前瞻性MGU数据库中，可以验证从CPRD数据集生成的观测值的假设生成的观测值。我们将验证OXCOM数据库中的初级保健prection模型。目标3：最近的观察结果表明，光链的异常变化分泌DBY MGUS患者可以帮助预测谁会发展为MGC，并且/或可能转化为骨髓瘤。与牛津化学系合作，我们可以预期评估从OXCOM服务获得的剩余患者样本中的这些初步观察结果。这些共享的研究资源将有助于在NHS中的早期诊断和MGUS/骨髓瘤护理方面的改善。我的愿景是在大数据分析（初级保健数据）（初级保健数据）中利用牛津的多学科专业知识，加入了二级保健临床服务和蛋白质化学的专业知识，以改善MGUS患者的监测，并提高MGC和MGC的早期诊断。

项目成果

Patient-reported symptoms and diagnostic journey in Multiple Myeloma.

• DOI: 10.3389/fonc.2023.1282569
• 发表时间: 2023
• 期刊: Frontiers in oncology
• 影响因子: 4.7

Monoclonal gammopathy of increasing significance: time to screen?

• DOI: 10.3324/haematol.2022.281802
• 发表时间: 2023-06-01
• 期刊: HAEMATOLOGICA
• 影响因子: 10.1
• 作者: Chen, Lucia Y.;Drayson, Mark;Bunce, Christopher;Ramasamy, Karthik
• 通讯作者: Ramasamy, Karthik