UNCOVER projects

Chronic Lymphocytic Leukaemia (CLL) is a chronic malignancy with excellent survival as a result of the introduction of highly specific and efficacious targeted therapy over the last decade. For diseases such as CLL, the data gathered by the UNCOVER project proves of immense value to understand the natural history of a chronic condition, which is otherwise impossible to extrapolate from single clinical trials. UNCOVER will also provide valuable data on the best treatment sequencing, the regional/demographical variations in the course of disease and the response to therapy. 

Finally, CLL patients also carry a risk of transformation to high grade lymphoma and secondary malignancies, which could also be appropriately addressed in a population dataset such as UNCOVER, that has longer follow-up that standard clinical trials.

All of the above are the initial objectives and projects of the CLL work package from UNCOVER. Our main goal is to provide the CLL community with relevant data that can aid treatment decision for CLL patients but also help regulators to make decisions in the best interest of our CLL patients.

Project outputs:

Conference poster presentation – International Workshop on CLL (IwCLL), 2025, ‘UNCOVER plus: A whole population dataset highlights inequalities in the diagnosis and survival of persons with chronic lymphocytic leukaemia in England’
 

Myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) are serious blood cancers that mainly affect older adults. Treatments often include intensive chemotherapy and stem cell transplants, which can lead to serious side effects, such as infections, regular hospital stays, long-term health problems, and in some cases, death. While most of the existing research has focused on how best to deliver chemotherapy, less attention has been paid to therapies designed to manage disease symptoms, known as supportive care.

Supportive care aims to improve the quality of life so that patients stay well enough to live at home. Several advocacy groups have made it clear that the ability to live independently, avoid unnecessary hospital time, and reduce side effects, are as important as survival.

Our aim is to better understand how both supportive care and intensive therapies are given and how these methods of delivery can be improved so that all MDS and AML patients in England are able to receive effective and person-centred treatment.

Project outputs:

TBD
 

TBC

Project outputs:

Conference presentation – 18th International Conference of Malignant Lymphoma (ICML), 2025, ‘Follicular lymphoma epidemiology and outcomes in England 2014-2021: preliminary analysis from the UNCOVER Study Group’

This work package is focussed on areas of limited evidence and unmet need in aggressive lymphoma. Our first project is analysing contemporary epidemiology and outcomes for primary central nervous system lymphoma, a highly morbid and resource intensive disease with recent treatment innovations. In addition to reporting outcomes overall and by treatment intensity, we are scrutinising the influence of socio-demographic factors such as comorbidity, deprivation and geography on disease incidence and survival. Future projects will include Burkitt lymphoma, another highly aggressive disease requiring in-patient intensive therapy. The group benefits from high quality PPI and clinical membership rotates allowing national experts in specific disease subtypes to maximise outcomes

Project outputs:

Conference poster presentation – 18th International Conference of Malignant Lymphoma (ICML), 2025, ‘Impact of Deprivation on Incidence and Outcomes of Primary CNS Lymphoma: A Nationwide English Cohort from the UNCOVER Study Group’
 

The multiple myeloma work package seeks to better understand frailty and its impact in the real world. The evidence base for disease outcomes in myeloma is largely derived from clinical trials, where frail patients are largely excluded. Analyses of this wealth of real-world data aims to better define frailty, establish socio-economic and geographical patterns associated with frail myeloma populations and explore the impact of frailty on treatment tolerability, disease outcomes and healthcare resource utilisation.

Project outputs:

• Conference poster presentation – 30th European Hematology Association (EHA) Congress, 2025, ‘Incidence and survival of multiple myeloma in England: an unselected cohort study from the UNCOVER Study Group and UKMRA Frailty Group.’
• Conference poster presentation – 22nd International Myeloma Society (IMS) Annual Meeting, 2025, ‘Frailty and social deprivation affect real-world outcomes in Multiple Myeloma (MM) – an England-wide cohort study from the UNCOVER Study Group and UKMRA Frailty Group.’
   

TBD

Work package 7 is looking at patients with Hodgkin lymphoma (HL), both classical HL and nodular lymphocyte predominant HL (NLPHL). Preliminary data analysis has taken place and identified 12,401 patients with cHL and 1,648 patients with NLPHL. In addition to incidence, data is available on age, sex, ethnicity and social deprivation as well as outcome data. 

Initial publication will focus on epidemiology with subsequent one on outcome data. Currently members of the group are deciding on which are most relevant questions to ask. We hope to obtain clinically useful real world population data in areas where it is difficult to find robust data e.g. treatment options and outcomes in NLPHL and management of elderly cHL.

Project outputs:

Conference abstract pending approval
 

TBD

Project outputs:

Conference abstract publication – 18th International Conference of Malignant Lymphoma (ICML), 2025, ‘Incidence and survival of mantle cell lymphoma (MCL) in England 2014-2021: a national cohort study from the UNCOVER Study Group’.

Marginal zone lymphomas (MZL) are a diverse group of slow growing lymphomas. Based on the predominant site they affect in the body, they are grouped into nodal (affecting lymph nodes), extra-nodal (affecting organs such as the stomach, salivary glands or lungs) and splenic (affecting the spleen). 

Taken together these lymphomas occur as commonly as follicular lymphoma. Some MZLs interestingly have a well-defined association with bacterial infections and can be treated with antibiotics. Most however are treated with more conventional lymphoma treatments such as radiotherapy, antibody therapy and/or chemotherapy. Some splenic MZLs may be treated with removal of the spleen although this has largely been replaced by systemic treatment. There are a number of questions that remain unanswered however within this group of slow growing lymphomas and our aim is to try and obtain some answers through the UNCOVER project. 

Our key objectives within this MZL work package are to define:

1. Demographics, incidence, ethnicity, socio-economic and geographical variation
2. Stage of disease at diagnosis
3. Co-morbidity index at diagnosis
4. Route to diagnosis for e.g. via GP or emergency presentation
5. Influence of age, sex, ethnicity, geographical region, year of diagnosis, co-morbidities and socio-economic status on 
a. Incidence
b. Overall survival
c. Relative survival
6. Above analysis by subtype of MZL – nodal, extranodal or splenic
7. The outcomes of patients in each subtype based on therapeutic intervention, derived by linking this data to the SACT (systemic anti-cancer therapy) database.

Project outputs:

TBD

TBD

TBD 

Project outputs:

Conference abstract and journal paper pending approval