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We respond to “promising” survival data from phase III trial of DCVax®-L

We respond to preliminary overall survival data from phase III clinical trial that suggests DCVax-L may help extend survival for patients with newly-diagnosed or recurrent glioblastomas.

An illustration of scientist who is a woman of colour looking down a microscope against a purple background.

Earlier this month, preliminary overall survival data from a major trial of DCVax-L in glioblastomas was presented at the New York Academy of Science’s ‘Frontiers in Cancer Immunotherapy 2022’ conference.

Delivered by Dr Paul Mulholland from UCLH in the UK, the results suggest that the phase III trial of 331 patients has found that DCVax-L may help extend survival for patients with newly-diagnosed or recurrent glioblastomas.

In newly-diagnosed glioblastomas, the data suggest that adding DCVax-L to treatment may offer patients nearly three months additional life on average, compared to temozolomide therapy alone – which could represent precious extra time to live.

However, while these appear to be really promising results, they are yet to be peer-reviewed and so need to be interpreted with caution at this stage.

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 a dendritic cell 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.

For some time now, experts have hoped that DCVax-L may represent the first emerging therapy proven effective in treating glioblastomas since temozolomide chemotherapy in 2005.

Where did the phase III trial take place?

Following encouraging results in phase I/II trials, an international phase III trial was established in 2007 – led by Dr Linda Liau at University of California, Los Angeles – which completed recruiting patients in November 2017.

The trial recruited 331 patients with newly-diagnosed glioblastoma across over 90 hospitals in the UK, US, Canada and Germany, making it one of the largest trials of a personalised cell therapy.

After surgery, 232 patients were randomised to receive DCVax-L plus standard temozolomide therapy, with 99 patients receiving placebo plus temozolomide.

Following disease recurrence, all patients initially receiving the placebo were then allowed to receive DCVax-L.

What has the trial shown?

The data suggest that adding DCVax-L to existing treatments may offer 2.8 months additional life on average for patients with newly-diagnosed glioblastomas.

The vaccine also seemed to be even more effective in patients with MGMT-methylated glioblastomas, for whom adding DCVax-L seemed to offer nearly 9 months additional life compared to the existing standard of care.

Overall, the trial data also suggests that:

  • DCVax-L doubled the five-year survival rate in newly-diagnosed patients, with 13% of patients in the trial being alive five years later, compared to just 5.7% of patients in the external control group taking the existing standard of care.
  • For recurrent glioblastoma, patients taking DCVax-L in the trial survived 13.2 months on average from recurrence, compared to 7.8 months on average among the external control group – an extension of 5.4 months compared to existing treatments.
  • The improvement in survival seemed to be significant in both patients under 65 and over 65, as well as in patients with significant residual disease after therapy.
  • The trial data also suggest DCVax-L may be very well tolerated by patients: out of 2,193 doses of the vaccine, five ‘severe adverse events’ occurred with no significant immune reactions.

Why do these results still need to be interpreted with caution?

While the results suggest DCVax-L may represent a long-awaited effective addition to treatment for glioblastomas, the trial data have yet to be peer-reviewed and published in a scientific journal.

One of the main reasons for even more caution until peer review is that the trial has involved a very innovative study design, which – as with all trials’ methodologies – needs to be independently validated by experts.

Firstly, when the trial was established in 2007, the primary ‘end point’ (the individual result) that the trial wanted to assess was whether adding DCVax-L to the standard of care would extend what is known as progression-free survival (the time until patients’ disease progressed and grew significantly).

However, it was later discovered that many patients experience something called ‘pseudo-progression’, whereby the body’s immune response make it look like the tumour has grown significantly – and imaging techniques can not sufficiently distinguish between the immune response and tumour growth.

It was therefore not possible to establish the impact of the vaccine on progression-free survival, and so the end-point of the trial was changed to overall survival (how long patients lived in total).

Secondly, the trial was established as a ‘crossover’ placebo-controlled trial, which meant that the patients who were initially randomised to the placebo group eventually then ‘crossed over’ to receive DCVax-L at the point their glioblastoma recurred – as it would be unethical for patients to undergo such an invasive procedure to extract immune cells from the blood for no potential benefit.

This meant that, when assessing the effect of the vaccine on overall survival in the trial, there was no longer a control group who had received a placebo to compare against – as there would traditionally be in randomised control trials.

The researchers therefore compared the results in those receiving DCVax-L to the survival of those in an ‘external control group’, selected from 15 parallel trials being run at similar institutions, who had received the same current standard of care.

What do UK experts think?

Dr David Jenkinson, Chief Scientific Officer at The Brain Tumour Charity, said:

The data presented are really promising and we now very eagerly await publication of the final results following peer review.

Glioblastomas remain the most common and most aggressive form of brain cancer and with so few treatments available, thousands affected by the disease in the UK each year are in urgent need of new options.

It is fantastic to see that many years of research and innovation may now be on the cusp of delivering a long-awaited new therapy for those living with glioblastomas.

We need to wait for these results to be independently validated, but we are now really hopeful that DCVax-L may represent the first new treatment able to offer life-extension to people living with a glioblastoma in over fifteen years.

Professor Michael Jenkinson, Professor of Neurosurgery at the University of Liverpool and Chair of the NCRI Brain Group, said:

The results of the dendritic cell vaccine trial hold real promise for patients with glioblastoma. This is the first drug trial since the introduction of temozolomide that has shown a meaningful improvement in survival, and that could represent the new standard of care for our patients.

Is DCVax-L available privately in the UK?

While the trial has not yet conclusively shown DCVax-L to be effective, the manufacturer 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. Anyone with questions about accessing the treatment privately should speak to their clinician in the first instance or contact the manufacturer directly at nwbio.com.

Anyone undergoing surgery for their glioblastoma may also wish to ensure their tumour tissue can be frozen without preservatives and without being embedded in paraffin blocks, in case they wish to consider DCVax-L treatment in the future.

Your questions answered

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.

The vaccine is administered by an intra-dermal injection in the arm (similar to a flu jab).

In order to produce DCVax-L, up to around 2g of frozen tumour tissue are usually required to make the eleven-shot three year cycle of DCVax-L injections. If tumour tissue has been frozen, it must have been saved without any chemicals or preservatives, and not in saline or blocks of paraffin. Unfortunately tumour banks and pathology departments frequently use paraffin or other preservatives that render the tissue unusable for the DCVax-L manufacturing process.

Some surgeons use Gliadel® wafers. These wafers are soaked with a type of chemotherapy which is meant to poison tumour cells, and are placed in the tumour cavity in the brain when the tumour is surgically removed. If Gliadel® wafers were used then DCVax-L is usually not a treatment option because the chemotherapeutic leaching from the wafer will also kill immune cells which enter the tumour cavity to fight residual tumour cells.

While the trial has not yet conclusively shown DCVax-L to be effective, the manufacturer 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. Anyone with questions about accessing the treatment privately should
speak to their clinician in the first instance or contact the manufacturer directly at nwbio.com.
Anyone with questions about their eligibility to access the treatment should speak to their clinician in the first instance.

In the first instance, please contact your clinician who will assess your suitability for DCVax-L.