A new combination of drugs to treat Primary Central Nervous System Lymphoma (PCNSL)

Primary Central Nervous System Lymphoma (PCNSL) is a rare but aggressive blood cancer that primarily affects the brain. This leads to serious issues like difficulty walking, seeing, remembering, speaking, and even seizures, which can have a big impact on someone’s quality of life. Most people diagnosed with this disease are older, with an average age of 69. PCNSL is usually first treated with chemotherapy, although this often doesn’t work or the cancer comes back. If the disease returns, many people have limited other effective treatment options. Current treatments, like additional chemotherapy or brain radiotherapy, rarely work and have severe side effects, meaning many people are left with the only option being palliative care. New treatments are urgently needed for people with this disease.

Researchers are building on the early success of a clinical trial called PRiZM+, which is testing new drugs for people with PCNSL that is hard to treat or people whose cancer has come back. One part of this trial showed promising results, with half of people responding to a drug called zanubrutinib.

In this project, Professor Fox and his team plan to add a new part to the trial to test a combination of three drugs: zanubrutinib, lenalidomide, and tafasitamab. These drugs work in different ways to target the cancer cells, and the researchers believe they could work even better together. They will recruit 20 new people who have seen PCNSL return to test how effective and tolerable this new combination drug treatment is. The researchers will also study samples from the trial to see if this drug combination could work as a treatment for other types of blood cancer, like diffuse large B cell lymphoma. They aim to develop less invasive ways to monitor how the disease progresses and how people respond to treatment.

This research could lead to better treatments and improved survival for people with relapsed PCNSL, who currently have few or no options. If this drug combination proves effective, researchers hope to conduct larger bigger clinical trials, so it eventually becomes an approved treatment for people with this disease.