The largest ever clinical trial looking at the best way to treat lymphoma if it spreads to the brain or spine has found that an intensive combination of chemotherapy and immunotherapy has meant patients who were given just months to live are alive and well years after diagnosis.

Treatment was even 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, and results like this have never been achieved before.

The findings from the international MARIETTA study could help contribute to a change in international guidelines on how to treat people after their lymphoma spreads to their brain or spine, known as secondary central nervous system lymphoma (SCNSL).

The UK arms of the trial were funded by Cancer Research UK’s Stand Up to Cancer campaign, and the results were published in Lancet Haematology.

SCNSL is rare but potentially lethal, and can develop in patients with diffuse large B-cell lymphoma, a type of aggressive blood cancer. Treatment for SCNSL hasn’t been well defined but previous small-scale trials have suggested high dose chemotherapy may be effective.

Because SCNSL is so rare, there aren’t enough patients in the UK for a clinical trial, so it’s been difficult to develop and test treatments.

For the MARIETTA study, researchers cast their net over a much wider area.

Led by Dr Kate Cwynarski from University College London Hospital in the UK and Professor Andres Ferreri in Milan, Italy, the trial assessed 75 patients across 24 centres in four countries, making it the largest trial ever to look at SCNSL.

Researchers believe that data gathered from a large number of patients with a wide geographical spread will mean the results are likely to be widely applicable.

Patients on the trial received a combination of chemotherapy and immunotherapy drugs in treatment regimens known as MATRIX and RICE.

Treatment included three courses of MATRIX followed by three courses of RICE, before a stem cell transplant using cells taken from the patients themselves.

Some patients on the trial also received a chemotherapy called R-CHOP before MATRIX-RICE if their cancer was life-threatening and had extensively spread to the spine or brain.

75 patients were assessed: 32 (43%) patients were initially diagnosed when their lymphoma had already spread to their brain or spine and had not received treatment, and 43 (57%) had previously been treated for lymphoma and the disease had spread after their cancer came back.

The trial achieved its measure of success, and MATRIX-RICE treatment prevented the cancer from worsening in 42 (58%) of the patients for at least one year after registering onto the trial. 100% of the patients who had the stem cell transplant had not seen their cancer worsen a year after registering onto the trial.

Whilst the MATRIX-RICE treatment was effective, 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.

In those patients, 2-year progression free survival was reported to be 71%, which has never been achieved before. Researchers say these results are extremely impressive because they are similar to those who have lymphoma that hasn’t spread to the brain or spine.

When patients were followed up at a median of 29 months after starting the trial, 32 did not have any worsening of their cancer and were still alive, with a 2-year progression free survival of 46% of patients, which increased to 83% for patients who received the transplant.

Overall, 56% experienced a serious adverse event, the most common being febrile neutropenia (fever and lower than normal levels of neutrophils, a type of white blood cell) and infections; and 95% of patients recovered, and four patients died due to infections.

The MARIETTA study suggests that this treatment programme could dramatically improve survival for patients with SCNSL, whilst highlighting the need to take into account whether patients had been treated prior to developing SCNSL.

As the largest trial of its kind, it could help contribute to a consensus on how to treat these patients in the UK and around the world.

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.”

Source: Cancer Research UK