The study, published in JAMA Oncology, found that in newly-diagnosed glioblastomas, adding DCVax-L to standard chemotherapy offered patients nearly three months additional life on average, compared to temozolomide therapy alone.
Glioblastomas are the most aggressive form of brain tumour in adults and have devastating effects for those diagnosed, with an average survival time of around 12-18 months following diagnosis.
What is DCVax-L?
It is a type of immunotherapy known as a dendritic cell vaccine. Developed by Northwest Biotherapeutics, DCVax-L is a personalised vaccine made from each patient’s own dendritic cells – a type of cell that helps the immune system recognise and attack cancer cells.
The process of making this vaccine involves taking both tumour cells and blood from the patient. Immune cells are separated from the patient’s blood and exposed to the tumour cells; it is through this process that dendritic cells learn to recognise the specific markers and proteins associated with the patient’s tumour cells.
The “educated” dendritic cells are then injected back into the patient, where they go on to recruit and “teach” other anti-cancer immune cells known as T-cells to travel to the tumour site and attack the cancerous cells.
Who was part of the trial?
331 patients, aged between 18 and 70 took part in this phase III clinical trial to investigate whether DCVax-L could offer a better treatment option for those diagnosed with glioblastoma.
Of the 331 patients, 232 patients were randomised in to the DCVax-L treatment group (DCVax-L and temozolomide chemotherapy) and 99 were randomised into the placebo group (temozolomide chemotherapy alone).
Within the placebo group, 64 patients had recurring glioblastoma and were subsequently crossed over to receive DCVax-L.
What has the trial shown?
The results from the phase III clinical trial have now been peer reviewed – a process by which other experts in the field review the work to ensure it is scientifically accurate.
The trial found that DCVax-L given in combination with temozolomide chemotherapy offered patients nearly three months of additional life on average, compared to standard chemotherapy alone.
The trial also found that DCVax-L doubled the five-year survival rate for those with a newly diagnosed glioblastoma, with 13% of patients being alive five years later, compared to 5.7% in the control group receiving the existing standard of care.
For those with recurrent glioblastoma, results were also promising with the 30 month survival rate doubling, with 11.1% of patients being alive after 30 months, compared to 5.1% in the control group.
Additionally, the results showed that patients who typically have poorer survival following a glioblastoma diagnosis, such as the elderly, those with tumour left behind after surgery or those with recurrent disease showed greater benefit from the DCVax-L treatment.
This novel treatment option was also proven to be safe for patients and could be used in combination with other treatments to offer patients a better chance of survival. It is also non-invasive for the patient and easy for a doctor to administer, it consists of six injections in the upper arm in the first year, and then twice a year for maintenance after that.
What do UK experts think?
Dr David Jenkinson, Chief Scientific Officer at The Brain Tumour Charity, said:
“This is a landmark and long-awaited breakthrough in the treatment of glioblastomas. It’s extremely exciting that adding this personalised vaccine to chemotherapy has been found to be able to offer nearly three precious extra months to live and spend time with loved ones to those diagnosed with the most aggressive form of brain cancer.
“With so few effective treatments available, average survival for the thousands diagnosed with a glioblastoma each year in the UK has for years remained heartbreakingly short at just 12-18 months. So it’s absolutely fantastic news that, following years of research and innovation, the first new systemic treatment able to offer life-extension to glioblastoma patients in over fifteen years has been found, and that it is effective in both newly-diagnosed patients and those with a recurrent tumour.
“The trial found that on average, the vaccine offered nearly three additional months of life, which could mean so much to many families, but it’s amazing to see that it also enabled twice as many people in the trial to still be alive five years after their diagnosis.
“We must now do everything we can to ensure this long-awaited hope is able to reach patients as soon as possible. Those facing the impossibly difficult diagnosis of a glioblastoma simply don’t have time to lose. It is critical that regulatory submission can now happen swiftly and that manufacturer Northwest Biotherapeutics works with NHS and drug appraisal bodies across the UK to ensure this new lifeline therapy can be made available to patients at a price the NHS can afford as soon as possible.
“Anyone affected by a glioblastoma can speak to us for support and information on 0808 800 0004 or by emailing email@example.com. If you need someone to talk to, we’re here for you.”
Professor Ashkan, Professor of Neurosurgery at King’s College Hospital, and European Chief Investigator of the clinical trial, said:
“Immunotherapy is a very promising approach for treating cancer, and the final results of this phase 3 trial, now unblinded and published, offer fresh hope to patients battling with glioblastoma.
“The vaccine was shown to prolong life, and interestingly so in patients traditionally considered to have poorer prognosis. For example, we see clear benefits in the older patient groups as well as in those patients in whom radical surgery was not possible for technical or other reasons.
“I am optimistic we can build upon this going forward; investigating combination of DCVax-®L with other emerging therapies for glioblastomas. The long-term survivor group in particular has the potential to further teach us about the basic biology of glioblastomas, given that many patients in this group did not have the usual expected characteristics for good outcomes.”
Your questions answered
The vaccine is administered by an injection in the arm (similar to a flu jab).
The process of making a dendritic cell vaccine is complex and involves taking both tumour cells and blood from the patient. Immune cells are separated from the patient’s blood and exposed to the tumour cells – it is through this process that dendritic cells learn to recognise the specific markers and proteins associated with the patient’s tumour cells. The “educated” dendritic cells are then injected back into the patient where they go on to recruit and “teach” other immune cells to recognise and attack the cancerous cells.
Northwest Biotherapeutics, the manufacturer of DCVax-L, announced in February 2022 that it was now able to produce the vaccine in the UK for individuals looking to access it privately. The list price of the treatment is not currently publicly available.
It is not yet clear where DCVax-L is available outside of the UK. However, the trial took place in the US, Canada, the UK and Germany.
If you have questions about accessing the treatment, speak to your clinician in the first instance or contact Northwest Biotherapeutics at https://nwbio.com/patients-information-form/.
Northwest Biotherapeutics, the manufacturer of DCVax-L, is currently preparing applications for regulatory approval of DCVax®-L, through the MHRA and NICE, which would need to happen before the treatment could be appraised for potential use on the NHS.
Unfortunately, these processes can take a long time so it is difficult to know for sure when this could be.
The trial involved people with either newly diagnosed or recurrent glioblastoma, so currently this is the only tumour type for which DCVax-L has been shown to be effective.
The production of DCVax-L requires up to around 2g of frozen tumour tissue. This means that your tumour needs to be operable or you need to have a frozen tissue sample from a previous operation. The tissue that is removed needs to go through a method of freezing known as flash freezing to be usable. Unfortunately tumour banks and pathology departments frequently use paraffin or other preservatives that render the tissue unusable for the DCVax-L manufacturing process.
For DCVax-L to be effective, your surgeon can not have used Gliadel® wafers during your surgery. This is because the wafers will have been soaked in chemotherapy, which will kill the immune cells which need to enter the tumour cavity in order for DCVax-L to work.
Speak to your clinician if you have further questions about this and whether you would be eligible.
There were very few side effects reported in the trial. Out of 2151 total doses of DCVax-L given, the trial reported just 5 adverse events which were related to the drug, none of which were immediately life threatening.