New clinical trials target aggressive form of blood cancer

Southampton researchers are launching two new studies for people with an aggressive form of lymphoma.

It’s hoped the clinical trials can improve survival and quality of life for patients whose cancer has come back or is resistant to current treatment.

Both the studies are focusing on immunotherapy treatment. These work by boosting the patient’s own immune system to help it find and destroy the cancer.

The trials are being run by the Southampton Clinical Trials Unit (CTU) based at the Centre for Cancer Immunology. They are led by Southampton’s Professor Andrew Davies.

A need for new treatments

Diffuse large B cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma where white blood cells, called B lymphocytes, begin to grow abnormally and cannot do their usual job of fighting infections in the body.

Around 5,500 people are diagnosed with DLBCL each year in the UK and will begin treatment.

“In around a third of patients, this first-line treatment will be unsuccessful,” says Professor Davies. “The lymphoma either does not respond or returns after initial slowing of the disease. In these cases, patients will need to start a second-line therapy.”

One of the second-line treatments currently used is a combination of chemotherapy and immunotherapy drugs called R-ICE followed by a stem cell transplant.

Professor Davies continues: “Unfortunately, around half of patients will still not respond to these treatments. We therefore need to look at additional approaches that can target this aggressive form of cancer and really benefit these patients.”

Boosting the immune system

The new trials are looking at whether adding an additional immunotherapy treatment can improve R-ICE therapy for DLBCL patients.

The P+R-ICE study involves pembrolizumab, a type of drug called a checkpoint inhibitor.

These drugs block a protein on the surface of immune cells which causes the cells to be switched off, and which can be used by cancer cells to stop the immune system from working properly. By blocking this protein, the T cell is stimulated into action and can seek out and destroy cancer cells.

Amber Cole, Trial Manager from P+R-ICE at the Southampton CTU, says: “Pembrolizumab is already used as a treatment for some other cancers such as melanoma and bladder cancer, as well as for Hodgkin lymphoma. Through the P+R-ICE trial we want to see whether it can also be an effective therapy to help improve outcomes for those with DLBCL as well.”

65 people will be recruited and randomly allocated into one of two trial arms. Two thirds will receive the R-ICE plus pembrolizumab, while those in the other arm will remain on R-ICE standard treatment. The trial opened to recruitment in July and has already recruited its first patients.

Funding for the P+R-ICE trial comes from a grant from Merck Sharp & Dohme (MSD).

International collaboration

The second study, Pola-R-ICE, is an international collaboration with a group in Germany. Centres are also taking part in Spain and Austria.

In this trial, an immunotherapy drug called polatuzumab vedotin is being added to R-ICE therapy. The treatment contains a cytotoxic drug that is attached to an antibody. This antibody seeks out and binds to a particular receptor on the surface of lymphoma cells. Once bound, it is taken inside the cell where the drug is released, causing the cancerous cell to be destroyed.

Professor Davies says: “Previous studies have shown that giving polatuzumab vedotin in combination with chemotherapy had promising activity in some patients with DLBCLs.

“334 patients will be recruited to this new trial with half receiving the Pola-R-ICE treatment, while a control group will be given R-ICE alone. We will then be able to see whether adding the immunotherapy treatment can improve response rates and survival for DLBCL patients where first-line treatment has not been successful.”

Pola-R-ICE is funded by a grant from Roche, with the UK arm of the study being endorsed by Cancer Research UK.