Clinical trial NCT05047107: Biology and Genetics of Smouldering Myeloma
Official title: Characterising Risk and Biology Of Smouldering Myeloma for Early Detection Of Symptomatic Myeloma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Smouldering Myeloma
MGUS
Multiple Myeloma
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
First posted: 2021-09-16
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any individual with a confirmed or suspected diagnosis of MGUS, SMM, or MM.

Brief summary: Observational clinical trial recruiting Smouldering Myeloma patients (SMM) or potential SMM patients. Study involves collecting blood and bone marrow samples to determine the features of the tumour genome and BM microenvironment, including immune dysfunction that are key drivers of progression from precursor conditions (MGUS and SMM) to MM.

Detailed description: MM is a cancer of plasma cells characterised by bone marrow infiltration by malignant plasma cells, kidney impairment, bone pain and elevated calcium levels1. There are approximately 5,500 new cases diagnosed annually in the UK, with a median survival of 5 years2. Significantly, despite improvements in conventional treatment options, MM remains incurable; patients inevitably relapse and will eventually die from their disease.3 MM is always preceded by defined precursor conditions, termed MGUS, and SMM. However, only 7% of MGUS patients and 50% of SMM patients progress to MM over a 5-year period4. In the UK, current practice favours commencing treatment only when there is evidence of end organ damage as the overall benefit of initiating early therapy is uncertain.

There is an increasing understanding that progression is determined by evolving changes in the tumour genome5 and changes in the immune microenvironment which support tumour growth, leading to progressively dysfunctional anti-tumour immunity. This project correlates changes in the tumour genome and immune microenvironment in individual patients with tumour progression and also aims to compare characteristics in patients with good and poor clinical outcomes with the objective of defining the drivers for disease progression. Furthermore, we aim to explore the use of blood samples to monitor tumour dynamics and immune function. Finally, we will also study the spatial distribution of immune cells and tumour cells in the bone marrow.

Clinical impact: A deeper understanding of the pathogenesis of MM will allow us to risk stratify patients with MGUS and SMM, and manage them accordingly as well as identifying subgroups of patients with MM who require different types of therapies, eg. more intensive multi-drug approaches for patients with adverse risk genetics.

Eligibility criteria: Inclusion Criteria:

* Any individual with a confirmed or suspected diagnosis of MGUS, SMM, or MM.

Exclusion Criteria:

* Patients under the age of 18
* Patients with active symptomatic myeloma at diagnosis
* Patients with no evidence of MGUS, sMM or MM
* Patients with rapidly rising paraprotein or serum free light chains suggestive of progressive disease at time of diagnosis or inclusion into study

Primary outcomes:
measure: Genomic markers of progression
timeFrame: 5 years
Secondary outcomes:
measure: Immune biomarkers
timeFrame: 5 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: University College London Hospitals
Study officials:
References: