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 (NHL) 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.

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 Low-grade non-Hodgkin lymphoma (NHL)
Developing novel therapeutics to cancer-selectively target the NF-kB pathway in Diffuse Large B-Cell Lymphoma
Professor Franzoso and colleagues have 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: CART-T therapy

Lead researcher - Professor Anastasios Karadimitris, Imperial College, London
Lymphoma High-grade non-Hodgkin lymphoma (NHL)
Chimeric antigen receptor-modified invariant NKT-cells for immunotherapy of CD1d+ B-cell malignancies
This team is modifying white blood cell called Natural Killer T cells so that they can selectively target two molecules found on the surface of lymphoma cells. Once the modified T-cell binds to CD19 on the surface of a lymphoma cell, a signal is sent to the body’s immune system to kill that cancer cell.

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 (NHL)
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.

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. 

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 Ajay Vora, University of Birmingham
Childhood acute lymphoblastic leukaemia (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 Burkitt lymphoma
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.

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
Diffuse large B cell lymphoma (DLBCL)
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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