High-grade non-Hodgkin lymphoma (HGNHL)

High-grade non-Hodgkin lymphoma (HGNHL)

High grade lymphomas usually grow more quickly and aggressively than low grade lymphomas.

The most common type of high-grade non-Hodgkin lymphoma (NHL) is diffuse large B-cell lymphoma (DLBCL). But there are a number of other types, including Burkitt lymphoma and peripheral T-cell lymphoma (PTCL).

Chemotherapy is commonly used to treat NHL, and for people with an early stage disease, this approach can be very effective. People who have later stage NHL usually receive chemotherapy with an added biologic therapy, such as rituximab. 

But not all people with NHL respond well to treatment, and many will relapse, so we urgently need to find new ways to treat these groups of people. 

We are supporting a portfolio of research into high-grade NHL across the UK. Our research aims to transform the way we diagnose and treat NHL, as well as searching for new treatments and tackling drug resistance.

Burkitt lymphoma

Burkitt Lymphoma is an extremely aggressive form of non-Hodgkin lymphoma, and treatment usually involves high intensity chemotherapy. Although this can help many people, some cannot tolerate this treatment as they are too frail, and this intensive approach may leave younger people with devastating life-long treatment effects.

Our research is focusing on finding new targeted treatment approaches, which could offer kinder and more effective treatment than conventional chemotherapy.

HOVON 127 BL trial

Chief investigator - Dr Andrew McMillan, University College London
High-grade non-Hodgkin lymphoma (HGNHL) Burkitt lymphoma
Phase III study comparing R-CODOX-M/R-IVAC versus dose-adjusted EPOCH-R (DA-EPOCH-R) for patients with newly diagnosed high risk Burkitt lymphoma Blood cancer type: Lymphoma/Burkitt lymphoma
Researchers want to find new ways to treat Burkitts lymphoma, and are comparing standard chemotherapy (R-CODOX-M or R-IVAC) with a different schedule (DA EPOCH-R) that appears to work well and has less side effects.

Predicting how well children and young adults with lymphoma respond to treatment

Lead researcher - Dr Amos Burke, Addenbrooke’s Hospital, Cambridge
Burkitt lymphoma
Determination of the prognostic significance of MDD and MRD in paediatric Burkitt lymphoma/leukaemia
Using samples from children and young adults with lymphoma who are on a clinical trial, Dr Burke will see how good two tests are at predicting treatment response. This research could lead to the development of a test that could predict how well a person will respond to their treatment.

Identifying new treatment strategies for leukaemia and lymphoma

Lead researcher - Professor Michelle West, University of Sussex
Acute myeloid leukaemia (AML) Burkitt lymphoma Hodgkin lymphoma
Analysis of PU.1 transcription control in leukaemia and lymphoma: towards new therapeutic strategies
Professor West and her team are investigating how the tight control of cell growth is lost in leukaemia and lymphoma cells. The team will look at the genetic changes that cause leukaemia, and will also look at how infection with the Epstein-Barr virus can cause lymphoma. Their aim is to identify new treatments and targets for drug development.

Developing kinder and smarter treatments for lymphoma

Our researchers are finding new ways to attack lymphoma by targeting the environment surrounding the lymphoma. They are also testing if drugs used for other blood cancers can be effective for people with lymphoma, developing new treatments and refining existing ones.

Can drugs for other blood cancers be used in lymphoma?

Lead researcher - Professor Guido Franzoso, Imperial College London
Lymphoma High-grade non-Hodgkin lymphoma (HGNHL)
Developing novel therapeutics to cancer-selectively target the NF-kB pathway in Diffuse Large B-Cell Lymphoma
Professor Franzoso and colleagues have previously developed a new cancer drug which they plan to trial in patients with multiple myeloma, an incurable blood cancer.  They reported how the drug, known as DTP3, kills myeloma cells in laboratory tests and mice, without causing any toxic side effects, the main problem with other cancer drugs. The new drug works by stopping a key process that allows cancer cells to outlive their normal lifespan and carry on multiplying.

New treatments for lymphoma: CAR-T therapy

Lead researcher - Professor Anastasios Karadimitris, Imperial College, London
Lymphoma High-grade non-Hodgkin lymphoma (HGNHL)
Chimeric antigen receptor-modified invariant NKT-cells for immunotherapy of CD1d+ B-cell malignancies
A type of white blood cell called an invariant Natural Killer T cell already targets a receptor called CD1d, which is found on the surface of lymphoma cells. Professor Karadimitris and his team are modifying these T cells so that they also selectively target another lymphoma receptor called CD19. By giving the T cells two receptors to target, they should exert a powerful anti-lymphoma effect, possibly more powerful than ordinary CAR-T cells.

Improving immunotherapy for blood cancer

Lead researcher - Professor Tim Illidge, University of Manchester
High-grade non-Hodgkin lymphoma (HGNHL)
Investigating the requirement for immunogenic cell death in the generation of anti-cancer immunity and eradication of haematological cancers
Professor Illidge and the team are exploring how dying cancer cells interact with the immune system, with the aim of improving how we combine chemotherapy and radiotherapy with immunotherapy when treating blood cancers.

Diffuse large B-cell lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma in the UK and is currently treated by chemotherapy together with an antibody therapy called rituximab. However, this approach is not always successful - many people do not respond, or only have a partial response.

Our researchers are looking at what drives DLBCL, and why some people do not respond to treatment. They are also searching for the molecular markers that can predict how a person will respond to treatment, which will help guide doctors with treatment decisions. Finding new drugs, and testing new treatment approaches in clinical trials also remains a focus.

Unmasking lymphoma

Lead researcher - Dr Graham Taylor, University of Birmingham
Lymphoma High-grade non-Hodgkin lymphoma (HGNHL)
Immune control of diffuse large B-cell lymphoma (DLBCL): prospective and retrospective studies on Epstein-Barr virus-positive disease
Dr Taylor wants to find out how lymphoma appears to avoid immune responses directed against it. Improving our understanding of these fundamental processes may lead to improved treatments for DLBCL that work by restoring or enhancing immune responses against the tumour.

COBALT trial

Chief investigator - Dr Karl Peggs, University College London
High-grade non-Hodgkin lymphoma (HGNHL)
Evaluating CAR19 as an optimal bridge to allogeneic transplantation
For the first time in the UK, Professor Peggs is running a trial that will use CAR-T therapy to reduce the amount of DLBCL cells present, so people can be well enough to undergo a stem cell transplant. He will be using a CAR-T therapy, which works by modifying a patient's T-cells to recognise a protein called CD19 found on the surface of lymphoma cells. 

TORCH trial

Chief investigator - Dr Graham Collins, Oxford University Hospitals NHS Trust
Lymphoma Diffuse large B cell lymphoma (DLBCL)
A phase II study to determine the safety and efficacy of the dual mTORC inhibitor AZD2014 and to investigate additional toxicities in combination with rituximab in relapsed refractory DLBCL
This trial is looking at a new biological therapy called vistusertib for people with diffuse B cell lymphoma (DLBCL) that has continued to grow during standard treatment of chemotherapy and rituximab, or has come back afterwards. 

Understanding how lymphoma cells hide from the immune system

Lead researcher - Dr Francesco Forconi, University of Southampton
High-grade non-Hodgkin lymphoma (HGNHL) Diffuse large B cell lymphoma (DLBCL)
Investigating surface Ig glycans of follicular and diffuse large B-cell lymphomas for diagnosis, prognosis and therapy
Dr Forconi and his team are exploring a sugar molecule that acts like a ‘tag’ on the surface of lymphoma cells that prevents it from being killed by the immune system. By understanding how the ‘tag’ works, researchers hope to find better and kinder ways to treat follicular lymphoma and diffuse large B cell lymphoma.

Finding better ways to manage the treatment of people with lymphoma

Targeted treatments – drugs that target specific pathways that drive cancer - are revolutionising treatment of many cancers. We’ve made lots of advances in lymphoma treatment by testing and introducing targeted treatments. But they don’t work for everyone, and that’s not always obvious before treatment is started. 

We have an ambitious project that aims to design a test that will tell doctors what the best available drugs are for an individual patient. We are also supporting a trial that wants to adjust chemotherapy that children are receiving for lymphoblastic lymphoma, so doctors can effectively treat the disease, but with reduced side-effects.

UKALL 2011

Chief investigator - Professor Pamela Kearns, University of Birmingham
Childhood acute lymphoblastic leukaemia (Ch-ALL)
UK Acute Lymphoblastic Leukaemia Trials
This trial is looking at treatment for children who have acute lymphoblastic leukaemia (ALL) or a type of non-Hodgkin lymphoma (NHL) called lymphoblastic lymphoma (LBL). Researchers want to see if using standard drugs in slightly different ways can achieve the same results but with fewer side effects, and reduce the risk of the blood cancer from returning. 

Peripheral T-cell lymphoma (PTCL)

Peripheral T-cell lymphoma (PTCL) is fast-growing, and needs to be treated quickly. People with PTCL are usually given a combination of chemotherapy drugs. For people who relapse after this course of treatment, there are limited treatment options available. We are supporting two clinical trials looking into new treatments for this group of people.

RomiCar trial

Chief investigator - Dr Graham Collins, Oxford University Hospitals NHS Trust
Lymphoma High-grade non-Hodgkin lymphoma (HGNHL)
A phase I/II study to determine the maximum tolerated dose and overall response rate of the combination of romidepsin and carfilzomib in relapsed or refractory peripheral T-cell lymphoma
People with peripheral T-cell lymphoma (PTCL) are usually given chemotherapy, but sometimes it continues to grow, or comes back after the treatment has finished. Researchers want to know if combining romidepsin - a HDAC inhibitor - and carfilzomib - a proteasome inhibitor - could help people with PTCL that has come back, or standard treatment has stopped working for them.

Finding better ways to diagnose and personalise treatments for people with PTCL

Lead researcher - Dr Matthew Ahearne, University of Leicester
Genetic markers from circulating DNA in PTCL - a RomiCar trial sub-study
At the moment, diagnosing and personalising treatments for peripheral T-cell lymphoma (PTCL) is done through a biopsy (taking a sample of tissue from the body), which can be painful and can’t easily be repeated during treatment. Dr Ahearne’s team are developing a new way to look for the genetic changes that are driving PTCL using blood samples to help overcome some of the difficulties with biopsies and improve diagnosis and personalised treatments.

Post-transplant lymphoproliferative disorders (PTLD)

Post-transplant lymphoproliferative disorders (PTLD) are lymphomas that sometimes occur after someone receives either a solid organ transplant, or a stem cell transplant.

Currently, patients are treated with rituximab and if they do not respond adequately after 7 weeks, receive additional treatment with a chemotherapy regime called R-CHOP. Although this strategy is often successful, many people do not respond or relapse.

We are supporting a trial that is testing if ibrutinib helps people with PTLD when added to standard chemotherapy.

Primary central nervous system lymphoma (PCNSL)

Peripheral central nervous system (PCNS) lymphoma is rare. These types of lymphomas start in the brain or spinal cord (central nervous system).

People with PCNS lymphoma are usually given chemotherapy with the biologic drug rituximab. This course of treatment often works well, but the outlook for the large proportion of people with PCNS lymphoma who relapse is poor. 

Our researchers are looking for new treatments in a clinical trial called TIER.

TIER trial

Chief investigator - Dr Christopher Fox, Nottingham University Hospitals NHS Trust
A phase I/II study of thiotepa, ifosphamide, etoposide and rituximab for the treatment of relapsed and refractory primary central nervous system lymphoma
Researchers are looking for new ways to treat people with PCNSL - a rare type of non-Hodgkin lymphoma that only affects the central nervous system. The trial is trying a new combination of cancer drugs comprising of chemotherapies and a biologic drug. 

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