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

基本信息

  • 批准号:
    MR/V037439/2
  • 负责人:
  • 金额:
    $ 12.48万
  • 依托单位:
  • 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

项目摘要

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事项,并可提高生存率:如果在最早期诊断,84%的骨髓瘤患者存活>5年,而如果在晚期诊断,则仅为26%。骨髓瘤最常被诊断为晚期(症状出现后>3-6个月),并且在任何癌症中具有最长的诊断延迟,在>30%的新诊断的骨髓瘤患者中具有紧急表现,这些患者缩短了生存期,骨髓产生的癌症是全球癌症死亡的第20大常见原因,并且仍然无法治愈。骨髓瘤(MM)通常在晚期被诊断出来,此时它对患者的整体健康有多种影响,包括骨骼疾病,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。骨髓瘤诊断和治疗越早,症状控制越有效,提高患者生存率,降低与治疗晚期骨髓瘤和伴随的合并症相关的医疗费用。每一种骨髓瘤都是由一种先前的、通常无症状的、未确诊的疾病引起的,这种疾病被称为意义不明的单克隆丙种球蛋白病(MGUS),发生在约3%的50岁及以上的人群中。筛查> 50岁的MGUS并使用现有的廉价诊断血液测试监测进展将使骨髓瘤早期诊断成为可能,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。临床意义的单克隆丙种球蛋白病(MGCS)是最近创造的术语,用于捕获一组具有肾损伤,神经损伤,与单克隆蛋白的存在或沉积直接相关的骨折或皮肤损伤。缺乏对这种临床关联的认识导致诊断延迟和对相关器官的不可逆损伤。因此,我们的目标是专门确定MGUS患者进展为骨髓瘤和/或MGCS的高风险。目标一:了解症状负担和驱动测试请求的其他临床参数,这使得MGUS的偶然诊断成为关键。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该数据集。我们将确定从MGUS到MM的转换的预测因子集。CPRD数据还将能够识别最近被描述为MGCS条件的临床关联。目标二:牛津大学医院,我们最近建立了OxCom临床服务,由牛津郡临床调试组资助,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缺乏对MGUS患者的连续随访的问题;患者经常失去随访,全科医生无法解决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具有详细临床和实验室数据的前瞻性数据集。可以在该前瞻性MGUS数据库中验证从CPRD数据集生成的假设生成观察结果。我们将在OxCom数据库中验证初级保健预测模型。目标三: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MGCS,和/或潜在地转化为骨髓瘤。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。这些共享的研究资源将有助于推动NHS早期诊断和MGUS/骨髓瘤护理的改善。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,以改善MGUS患者的监测,并实现MGCS和骨髓瘤的早期诊断。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Patient-reported symptoms and diagnostic journey in Multiple Myeloma.
  • DOI:
    10.3389/fonc.2023.1282569
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    4.7
  • 作者:
  • 通讯作者:
Monoclonal gammopathy of increasing significance: time to screen?
  • DOI:
    10.3324/haematol.2022.281802
  • 发表时间:
    2023-06-01
  • 期刊:
  • 影响因子:
    10.1
  • 作者:
    Chen, Lucia Y.;Drayson, Mark;Bunce, Christopher;Ramasamy, Karthik
  • 通讯作者:
    Ramasamy, Karthik
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Karthik Ramasamy其他文献

Health-Related Quality of Life for Frail Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab, Lenalidomide and Dexamethasone: Subgroup Analysis of MAIA Trial
  • DOI:
    10.1182/blood-2022-165524
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
  • 作者:
    Aurore Perrot;Thierry Facon;Torben Plesner;Saad Usmani;Shaji K Kumar;Nizar Jacques Bahlis;Cyrille Hulin;Robert Z. Orlowski;Hareth Nahi;Peter Mollee;Karthik Ramasamy;Murielle Roussel;Arnaud Jaccard;Michel Delforge;Lionel Karlin;Bertrand Arnulf;Ajai Chari;Huiling Pei;Niodita Gupta;Shuchita Kaila
  • 通讯作者:
    Shuchita Kaila
Impact of Autologous Stem Cell Transplant (ASCT) Versus Consolidation on Health-Related Quality of Life (HRQoL) for Patients with Multiple Myeloma Receiving Carfilzomib Maintenance: Results from the Cardamon Trial
  • DOI:
    10.1182/blood-2022-166344
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
  • 作者:
    Rakesh Popat;William Wilson;Marquita Camilleri;Karthik Ramasamy;Matthew Streetly;Jonathan Sive;Ceri Bygrave;Reuben Benjamin;Michael A Chapman;Selina J Chavda;Beth Phillips;Maria del Mar Cuadrado;Gavin Pang;Richard Jenner;Tushhar Dadaga;Sumaiya Kamora;Ruth M. de Tute;James Cavenagh;Laura Clifton-Hadley;Roger G Owen
  • 通讯作者:
    Roger G Owen
OAB-018: From CARDAMON to CoMMpass: a mutational signature that predicts carfilzomib-specific outcomes in myeloma
  • DOI:
    10.1016/s2152-2650(22)00291-9
  • 发表时间:
    2022-08-01
  • 期刊:
  • 影响因子:
  • 作者:
    Ieuan Walker;Garima Khandelwal;Venetia D’Arcy;William Wilson;Evie Fitzsimons;Daria Galas-Filipowicz;Rakesh Popat;Karthik Ramasamy;Matthew Streetly;Ceri Bygrave;Reuben Benjamin;Ruth de Tute;Marquita Camilleri;Selina Chavda;Gavin Pang;Richard Jenner;Tushhar Dadaga;Sumaiya Kamora;James Cavenagh;Laura Clifton-Hadley
  • 通讯作者:
    Laura Clifton-Hadley
Mezigdomide (CC-92480), a Potent, Novel Cereblon E3 Ligase Modulator (CELMoD), Combined with Dexamethasone (DEX) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results from the Dose-Expansion Phase of the CC-92480-MM-001 Trial
  • DOI:
    10.1182/blood-2022-157945
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
    23.100
  • 作者:
    Paul G. Richardson;Suzanne Trudel;Hang Quach;Rakesh Popat;Sagar Lonial;Robert Z. Orlowski;Kihyun Kim;María-Victoria Mateos;Charlotte Pawlyn;Karthik Ramasamy;Joaquín Martinez-Lopez;Alessia Spirli;Ignacio Casas-Avilés;Jing Gong;Michael Amatangelo;Jessica Katz;Paulo Maciag;Teresa Peluso;Nizar J. Bahlis
  • 通讯作者:
    Nizar J. Bahlis
Tumour-intrinsic features shape T-cell differentiation through myeloma disease evolution
肿瘤内在特征通过骨髓瘤疾病进化塑造 T 细胞分化
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    K. Foster;Elise Rees;L. Ainley;Eileen M. Boyle;Lydia Lee;Gwennan Ward;D. Galas;Anna Mikolajczak;Emma J Lyon;Dylan Jankovic;Jasmine Rahman;Mahima Turakhia;Imran Uddin;Gordon Beattie;Yvette Hoade;Catherine Zhu;J. Reading;Ieuan G Walker;Michael Chapman;Karthik Ramasamy;Javier Herrero;B. Chain;S. Quezada;Kwee Yong
  • 通讯作者:
    Kwee Yong

Karthik Ramasamy的其他文献

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{{ truncateString('Karthik Ramasamy', 18)}}的其他基金

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
  • 财政年份:
    2021
  • 资助金额:
    $ 12.48万
  • 项目类别:
    Research Grant

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