Dr Alasdair Rankin
Director of Research and Policy, Blood Cancer UK
CAR-T therapy is one of the most exciting advances in cancer treatment in recent years, potentially providing a cure when all other drugs have failed. But, currently, its use is limited to a small group of patients
Only six children with acute lymphoblastic leukaemia (ALL) and 75 adults with diffuse large B-cell lymphoma (DLBCL) were treated with CAR-T therapy by the NHS in England between October 2019 and March 2020, according to official data.
Cost often means CAR-T therapy is a last resort
CAR-T therapy works by taking T cells from the patient and changing them to produce new proteins on their cell surface, allowing them to seek out and destroy cancer cells.
The NHS funds its use for three types of blood cancer – and only when all other treatment options have been exhausted.
Therefore, the number of people who can benefit from CAR-T at the moment is quite small – a message that was perhaps lost in the media fanfare when it was made available in late 2018.
There are several issues that need to be addressed if CAR-T therapy is to be used more widely and perhaps the most obvious one is cost.
CAR-T therapies are manufactured for each individual patient using their own cells, making them very expensive.
Could CAR-T therapies be mass-produced?
Blood Cancer UK is funding a team led by Professor Waseem Qasim at University College London, who is looking at how to ‘edit’ DNA carried by T cells to allow CAR-T cells to attack cancerous T cells.
Not only would this allow CAR-T therapies to treat more types of blood cancer – their use so far has been mainly restricted to treating cancers that start in B cells – it could also make CAR-T therapies ‘universal’.
Using one batch of CAR-T cells to treat many patients would make the treatment significantly cheaper.
Treating a wider range of blood cancers
The CAR-T therapies currently approved to treat childhood ALL and DLBCL are engineered to recognise a protein called CD19, which is found in large numbers on the surface of these cancer cells.
We may see CD19 CAR-T used more widely as trials investigate its use in other B cell cancers, and at earlier stages of treatment.
But another challenge has been to design effective CAR-T therapies to target cancer cells that do not have such a common protein on their surface.
CAR-T therapies are manufactured for each individual patient using their own cells, making them very expensive.
At Blood Cancer UK, we funded one part of this story – early research into a new CAR-T therapy for myeloma that targets a common protein found on myeloma cells called BCMA and another protein at the same time.
This promising approach of targeting multiple proteins on a cancer cell in order to increase response rates is becoming more common in CAR-T therapy development.
Clinical trials for CAR-T therapies that target the BCMA protein on myeloma cells are starting to show promise.
Results from several trials for CAR-T therapies that target BCMA in different ways were announced at the American Society of Hematology Annual Meeting in December 2019, with positive early responses from patients.
These therapies face challenges to prove their long-term effectiveness, but CAR-T therapy to treat myeloma is currently undergoing assessment for approval by the FDA in America.
What is next for CAR-T therapy?
A new type of CD19 CAR-T therapy for mantle cell lymphoma is being assessed for use on the NHS this year. This is a blood cancer with a clear, unmet patient need, with only around four in 10 people currently surviving longer than five years.
CAR-T therapy is also expected to be assessed as a treatment for people with DLBCL who have relapsed or not responded to just one form of standard treatment, potentially extending its use.
With a review also due on whether the two CAR-T therapies currently available through the Cancer Drugs Fund should be made permanently available on the NHS in England, there will be more tough decisions for NICE to make as they weigh the value of these expensive treatments that we know can provide a lifeline for people with blood cancer.
