Cancer is an extremely complex disease. There are over 200 different types, some of which are considered common and others which are classified as rare cancers. But what exactly does it mean if a cancer is rare?
Usually, it means it only affects a small handful of people, but doctors might also call a cancer rare if it starts in an uncommon place in the body, or if the cancer is an unusual type and requires special treatment.
For secondary central nervous system (CNS) lymphoma, its an incredibly rare cancer for a combination of these reasons.
Secondary CNS lymphoma is a type of lymphoma thats spread to the brain and spinal cord nervous system after originating elsewhere in the body. And as well as being a rare cancer, secondary CNS lymphoma is an aggressive cancer, which has relatively low survival rates.
However, the latest results from the Stand Up To Cancer-funded MARIETTA clinical trial, which details a new potentially transforming treatment, has shed a glimmer of hope for patients and doctors alike.
We spoke to Dr Kate Cwynarski, who led the study in the UK, about what the latest results could mean for patients with secondary CNS lymphoma.
With a rare cancer such as secondary CNS lymphoma, finding a large enough group of patients can be a real challenge. And in cases like this, researchers have to think on a global scale.
Its a rare disease. So the reality of it is that you would not get this information if we just performed a trial in the UK, says Cwynarski. International collaboration is the only way to do it.
The MARIETTA trial is the largest study focused on patients with secondary CNS lymphoma, involving 24 centres across 4 countries and recruiting a total of 79 patients. It involved the International Extranodal Lymphoma Group (IELSG) lead by Professor Andres Ferreri in Italy and it built on the success of prior research with this group. In the UK, the trial was managed by CRUK Southampton CTU.
In particular, findings from a previous clinical trial partly funded by us, which tested treatments for primary CNS lymphoma, a lymphoma thats only found in the brain, helped inform the design of this clinical trial.
The IELSG-32 trial tested the benefits of an intensive chemotherapy regimen known as MATRIX, followed by either whole brain radiotherapy or a stem cell transplant using the patients own cells.
Cwynarski describes the IELSG-32 trial as practice changing, and its from these impressive results that the MARIETTA trial was developed. So we adapted a strategy that was successful in treating primary CNS lymphoma in the IELSG-32 trial and added another chemotherapy regimen, called R-ICE, to help treat the systemic disease on top of the secondary brain disease.
Cwynarski specialises in lymphoma, so she has treated SCNSL patients both on and off the trial. One of the big benefits of this trial, she describes, is that the inclusion criteria for the cohort more accurately reflected the patients she sees in her clinic and referral practice.
This trial included patients up to 70 years of age. And it wasnt just focused on fit, young people. So I have to say I think it was meaningful, because it included the kind of patients that we actually see.
The trial also included people regardless of when their secondary CNS lymphoma was diagnosed, whether that was when someone was originally diagnosed with lymphoma, during treatment, or after their cancer had come back.
And the results look promising. A total of 49 patients (65%) responded to the treatment in some way, with 37 people going on to have a stem cell transplant. 100% of the patients who had the stem cell transplant had not seen their cancer recur a year after registering onto the trial. We are optimistic many will be cured of this aggressive lymphoma.
But the trial also picked up differences between groups. While the regime was effective to an extent in every sub-group, the most significant results were seen in patients whose CNS disease was discovered at initial lymphoma diagnosis. Within this group, 71% of patients had lived for 2 years without their cancer growing.
A result which has never been seen before.
The results of the trial have completely transformed the teams optimism when meeting new patients. We really have identified a regimen which is intensive, but its potentially curative, concludes Cwynarski, and the word cure is not something weve really used before when talking about this disease.
Recently, Cwynarski has been busy filling out a cohort of her patients DVLA forms, confirming they are fit to drive again after being 2 years treatment free. So thats an amazing success and it was very symbolic as a reminder that these people have been alive and off all treatment for 2 years.
Moments like this are a reflection of the huge impact the MARIETTA trial has had for real people, like Maureen Brewster.
Maureen was diagnosed with lymphatic cancer of the liver in 2011 and was under the watchful eyes of a consultant during her treatment. But in the summer of 2016, I started to have very extreme headaches, says Maureen.
After getting an emergency appointment, she was taken to A&E and admitted to hospital straight away. I was transferred to the National Neurology hospital in Russell Square for a biopsy. They thought I might have had a stroke. But it wasnt. Instead, Maureen was diagnosed with a secondary cancer in her brain.
When Maureen was transferred to UCLH, she was told about the MARIETTA trial. I could have chosen not to go on the trial, but being part of it meant that I would get more examinations and monitoring. So it was more reassuring to be on the trial, she says.
Maureen during treatment.
Maureen went through 8 tough months of chemotherapy before having a stem cell transplant in the summer of 2017. During one round of chemo in the hospital I became ill with an infection and really thought I was going to die. The last chemo prior to me having stem cell transplant was so strong it really had an impact on me and I couldnt eat I felt very poorly for a few weeks.
Maureens stem cell transplant went smoothly and prior to COVID-19, she was having regular check-ups and scans in hospital.
Prior to the first lockdown in March 2020, Maureen was able to do some volunteering and also go back to work, teaching a course on Project Management at a local adult college. In April 2019 I also secured a part-time job as a User Involvement Co-ordinator. It was great to get back to that level.
Dr Cwynarski emphasises that while the trial was a great success for some, it also exposed a group of patients who didnt do so well on the treatment.
The results threw up a real disparity and uncovered an unmet need in a particular group of patients. For the group of patients whose cancer had already failed to respond to a chemotherapy treatment, known as R-CHOP, at the follow up of 2 years, only 20% had not experienced their cancer progressing or getting worse.
We need to target this cohort of patients in a different way, says Cwynarski. So really the challenge is, can we identify experimental agents be it different biological agents or immunotherapies such as CAR T cell therapy in the patients who have relapsed, and maybe bringing these therapies into the frontline.
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