Largest clinical trial for rare blood cancer points towards improved survival

A combination of chemotherapy and immunotherapy could be key to treating lymphoma that has spread to the brain or spine, according to a new study published Lancet Haematology. 

The results come from the largest ever clinical trial looking at how to treat lymphoma when it has spread to the brain or the spine. Findings from the international MARIETTA study showed that treatment was more effective in patients whose lymphoma had spread to the brain when first diagnosed, compared with those who had previously been treated for lymphoma and the disease had spread after their cancer came back. 

The study took place in the UK, Italy, Switzerland and Netherlands, with the UK arms of the trial managed by the Cancer Research UK Southampton Clinical Trials Unit in the UK and the International Extranodal Lymphoma Studies Group (IESLG) internationally.

The findings could potentially help inform international guidelines on how to best treat people after their lymphoma spreads to their brain or spine. Also known as secondary central nervous system lymphoma (SCNSL), SCNSL is rare and potentially lethal, developing in patients with diffuse large B-cell lymphoma, which is an aggressive form of blood cancer. 

The rarity of SCNSL has meant that treatments have been difficult to develop, due a lack of patients for a large-scale clinical trial. The MARIETTA study was able to assess 75 patients across 24 centres, with the researchers believing that the data gathered from this number of patients, across a wide geographical spread, will be widely applicable. 

During the trial, patients received a combination of chemotherapy and immunotherapy drugs, which varied depending on the severity of their cancer. Stem cell transplants were also performed using cells taken from the patients themselves. 

When the patients were assessed, 32 were initially diagnosed when their lymphoma had already spread to their brain or spine and had not yet received treatment. The remaining 43 had previously been treated for lymphoma and the disease had spread after their cancer came back. 

The combination of chemotherapy and immunotherapy prevented the cancer from worsening in 42 of the patients for at least one year after registering onto the trial. All of the patients who had the stem cell transplant had not seen their cancer worsen a year after registering onto the trial.

The trial found that those whose lymphoma had spread to the brain or spine when first diagnosed responded far better than those who had been treated for lymphoma already. For those patients, their two-year progression free survival was reported at 71%, a figure which the researchers say has never been achieved before. 

Patients were followed up after a period of 29 months after starting the trial. At this point, 32 did not have any worsening of their cancer and were still alive. Overall, a two-year progression free survival was reported in 46% of patients, which increased to 83% for patients who received the transplant.

Over half (56%) of the patients experienced a serious adverse event with the most common being febrile neutropenia. Four patients died due to infections.  

Maureen Brewster, a patient who took part in the trial, said: “I was diagnosed with a brain tumour in 2016 after originally having lymphoma in 2011, and feel incredibly grateful to have been on the MARIETTA trial. Being on the trial meant that my health and treatment course was closely monitored. I also had the opportunity to try out a new treatment course that, at the end of the day, means I’m still alive and have since been able to return to work and enjoy life.”

Dr Kate Cwynarski, a consultant haematologist at University College London Hospital and one of the lead researchers for the trial, said: “The MARIETTA trial has meant patients who may have had just months to live are alive and living well years after being diagnosed. It is incredible to be able to sign DVLA forms for many of my patients treated with this approach, as you can’t drive until you have been clear of treatment for two years and are well, which really brought home the impact this study has had.”

Michelle Mitchell, chief executive of Cancer Research UK, said: “We’re dedicated to improving outcomes for all cancer patients, but it can be incredibly difficult to make progress and develop new treatments for rare cancers. As we’ve seen during the Covid-19 pandemic, international collaboration is needed to tackle research challenges that can’t be faced alone, and the MARIETTA trial is a great example of this.”