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First large-scale study in diffuse large B-cell lymphoma to use real-time molecular characterisation

Published: 10 April 2019

Lymphoma is a cancer of cells of the immune system. It develops when lymphocytes (a type of white blood cell) start to divide in an uncontrolled way. Professor Andy Davies has published the first large scale study in diffuse large B-cell lymphoma to use real-time molecular characterisation in Aprils Lancet Oncology.

Lymphoma is a cancer of cells of the immune system. It develops when lymphocytes (a type of white blood cell) start to divide in an uncontrolled way. Lymphomas are divided into 2 main groups; Hodgkin lymphoma and non-Hodgkin lymphoma (NHL), which behave differently and need different treatment. Diffuse large B-cell lymphoma (DLBCL) is the most common type of high-grade (fast-growing) non-Hodgkin lymphoma.

The randomised evaluation of molecular guided therapy for diffuse large B-cell lymphoma with bortezomib (REMoDL-B) study aimed to investigate the clinical efficacy of bortezomib in addition to R-CHOP in patients with diffuse large B-cell lymphoma. To determine whether the cell-of-origin subtypes respond differently to the combination of bortezomib with R-CHOP, we used a study design that incorporated prospective randomisation stratified by whole transcriptome gene-expression profiling.

As clinical studies move towards increased application of targeted drugs against molecular phenotype, the feasibility of determining a molecular phenotype in real-time was an important objective of the study and REMoDL-B is the first large-scale study in diffuse large B-cell lymphoma to use real-time molecular characterisation. The study has been published this month in Lancet Oncology.

 

Professor Andy Davies, Consultant in Medical Oncology within Medicine at the University of Southampton, said: “The trial design provides a rational framework for future studies in diffuse large B-cell lymphoma, allowing prompt initiation of treatment while molecular characterisation is carried out. We confirm that R-CHOP is a good standard of care for most patients with diffuse large B-cell lymphoma, but raise the possibility that high-risk subgroups could benefit from the addition of a proteasome inhibitor to standard therapy, which could guide future research”.

 

The REMoDL-B trial was funded by CRUK1 Jannsen Cilag2 (pharmaceutical company) and Bloodwise Charity3 as an Investigator Initiated Study. The trial was sponsored by UHS NHS trust5 and was managed though the Southampton Clinical Trials Unit4 (SCTU). The SCTU is based in the new Centre for Cancer Immunology (CCI) 6, which opened recently following a successful public funding campaign.

 

1. Cancer Research UK www.cancerresearchuk.org/ is the worlds largest cancer charity. Their vision is to bring forward the day when all cancers are cured. They aim is to accelerate progress in cancer treatment and see three-quarters of people surviving the disease within the next 20 years.
 

2. Jannsen Cilag www.janssen.com/uk/ Janssen is one of the world’s leading research-based pharmaceutical companies and is part of the Johnson & Johnson family of companies – the largest diversified healthcare group in the world.
 

3. Bloodwise Charity www.bloodwise.org.uk/  are a leading blood cancer charity who fund research to change the lives of people living with leukaemia, lymphoma, myeloma and other blood cancers.
 

4. The Southampton Clinical Trials Unit (SCTU) www.southampton.ac.uk/ctu/ is a UKCRC registered CTU with expertise in the design, conduct and analysis of multicentre interventional clinical trials. We work in partnership with investigators to deliver high quality trials that will directly influence routine clinical practice. 
 

5. University Hospital Southampton NHS Foundation Trust is one of the largest acute teaching trusts in England, with an annual spend of £700 million at three sites across the city of Southampton. It provides hospital services for 1.9 million people living in Southampton and southern Hampshire. With specialist services including neurosciences, respiratory medicine, cancer, cardiovascular, obstetrics and specialist children’s services to more than 3.7 million people in central southern England and the Channel Islands. Every year more than 10,500 staff, including more than 700 consultants, professors and senior lecturers, see 585,000 people at outpatient appointments, deal with 120,000 attendances at the emergency department and treat 150,000 admitted emergency, inpatient or day case patients. In addition, the Trust delivers more than 100 outpatient clinics across the South of England to keep services local for patients. Providing these services costs £1.9 million per day.
 

6. Building on its cancer immunology research expertise and recent successes in immunotherapy trials, the University of Southampton has completed a major fundraising campaign to raise £25m to open the UK’s first dedicated Centre for Cancer Immunology at Southampton General Hospital in 2017.  The Centre is the first of its kind in the UK and will bring together world-leading specialists in a unique state-of-the art centre.  The aim of the new centre is to accelerate research progress, conduct more clinical trials and save more lives from cancer.  Find out more about it at www.southampton.ac.uk/youreit

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