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/V037439/1
• 负责人: Karthik Ramasamy
• 金额: $ 27.95万
• 依托单位: Oxford University Hospitals NHS Trust
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV037439%2F1
• 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.

早期检测对于患者来说是重中之重，可以提高生存率：如果在最早阶段得到诊断，84% 的骨髓瘤患者的生存期超过 5 年，而如果在晚期诊断，这一比例仅为 26%。骨髓瘤最常被诊断为晚期（症状出现后 >3-6 个月），并且是所有癌症中诊断延迟时间最长的，超过 30% 的新诊断骨髓瘤患者会出现紧急症状，这些患者的生存期会缩短（由骨髓引起的癌症）。是全球第 20 位最常见的癌症死亡原因，并且仍然无法治愈。骨髓瘤 (MM) 通常在晚期才被诊断出来，此时它会对患者的整体健康产生多种影响，包括骨病、肾脏疾病和免疫系统减弱。最近的治疗提高了预期寿命和生活质量。骨髓瘤越早诊断和治疗，症状就能得到更有效的控制，从而提高患者的生存率并降低与治疗晚期骨髓瘤和伴随并发症相关的医疗费用。每一种骨髓瘤都源于一种称为意义未明的单克隆丙种球蛋白病 (MGUS) 的前期疾病，这种疾病通常无症状且未确诊，约 3% 的 50 岁及以上人群发生该病。对 MGUS 进行 50 秒以上的筛查并使用现有的廉价诊断血液检测监测进展将有助于骨髓瘤的早期诊断，但不太可能具有成本效益，因为大多数 MGUS 患者不会发展为 MM。具有临床意义的单克隆丙种球蛋白病（MGCS）是最近创造的一个术语，用于描述一组患有与单克隆蛋白的存在或沉积直接相关的肾功能不全、神经损伤、骨折或皮肤损伤的单克隆丙种球蛋白病患者。缺乏对这种临床关联的认识会导致诊断延迟并对相关器官造成不可逆转的损害。因此，我们的目标是专门识别进展为骨髓瘤和/或 MGCS 高风险的 MGUS 患者。目标 1：了解症状负担以及推动测试请求的其他临床参数，这是偶然诊断 MGUS 的关键。使用对编码为单克隆丙种球蛋白病的患者的临床实践研究数据链接 (CPRD) 初级保健记录的访问来生成此数据集。我们将确定从 MGUS 到 MM 转换的一组预测变量。 CPRD 数据还将能够识别最近描述为 MGCS 状况的临床关联。目标 2：牛津大学医院，我们最近在牛津郡临床调试小组的资助下建立了 OxCom 临床服务，以改善牛津郡社区患者的连续 MGUS 监测。这笔资金已分配用于解决 MGUS 患者缺乏连续随访的问题；患者经常无法进行随访，全科医生也无法解决 MGUS 患者在初级保健中产生的临床问题。 OxCom 基础设施使我们能够生成包含详细临床和实验室数据的前瞻性数据集。从 CPRD 数据集生成的假设生成观察结果可以在这个前瞻性 MGUS 数据库中得到验证。我们将验证 OxCom 数据库中的初级保健预防模型。目标 3：最近的观察表明 MGUS 患者分泌的轻链的异常变化可以帮助预测谁会发展为 MGCS，和/或可能转化为骨髓瘤。与牛津大学化学系合作，我们可以前瞻性地评估从 OxCom 服务获得的剩余患者样本中的这些初步观察结果。这些共享的研究支持资源将有助于推动 NHS 的早期诊断和 MGUS/骨髓瘤护理的改进。我的愿景是利用牛津大学跨大数据分析（初级护理数据）的多学科专业知识，联合二级护理临床服务和蛋白质化学专业知识可改善 MGUS 患者的监测，并实现 MGCS 和骨髓瘤的早期诊断。

项目成果

Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper.

冒烟性骨髓瘤的诊断和治疗：英国血液学会良好实践论文。

• DOI: http://dx.10.1111/bjh.19333
• 发表时间: 2024
• 期刊: British journal of haematology
• 影响因子: 6.5
• 作者: Hughes D

Prospective Assessment of Tumour Burden and Bone Disease in Plasma Cell Dyscrasias Using DW-MRI and Exploratory Bone Biomarkers.

使用 DW-MRI 和探索性骨生物标志物对浆细胞失调中的肿瘤负荷和骨疾病进行前瞻性评估。

• DOI: http://dx.10.3390/cancers15010095
• 发表时间: 2022
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Agarwal G

Monoclonal gammopathy of increasing significance: time to screen?

单克隆丙种球蛋白病的重要性日益增加：是时候进行筛查了吗？

• DOI: http://dx.10.3324/haematol.2022.281802
• 发表时间: 2023
• 期刊: Haematologica
• 影响因子: 10.1
• 作者: Chen LY

Multiple myeloma screening within a fracture liaison service (FLS).

骨折联络服务 (FLS) 内的多发性骨髓瘤筛查。

• DOI: http://dx.10.1007/s00198-021-06233-6
• 发表时间: 2022
• 期刊: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
• 作者: Agarwal G

Patient-reported symptoms and diagnostic journey in Multiple Myeloma.

多发性骨髓瘤患者报告的症状和诊断过程。

• DOI: http://dx.10.3389/fonc.2023.1282569
• 发表时间: 2023
• 期刊: Frontiers in oncology
• 作者: Vijjhalwar R